MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'American Journal of Physiology. Lung Cellular and Molecular Physiology' source. Tue, 07 Feb 2012 08:48:50 +0100 http://www.medworm.com/index.php?rid=5659140&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22287606%26dopt%3DAbstract Authors: Tanjore H, Blackwell TS, Lawson WE Abstract While the factors that regulate the onset and progression of idiopathic pulmonary fibrosis (IPF) are incompletely understood, recent investigations have revealed that endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) are prominent in alveolar epithelial cells in this disease. Initial observations linking ER stress and IPF were made in cases of familial interstitial pneumonia (FIP), the familial form of IPF, in a family with a mutation in surfactant protein C (SFTPC). Subsequent studies involving lung biopsy specimens revealed that ER stress markers are highly expressed in the alveolar epithelium in IPF and FIP. Recent mouse modeling has revealed that induction of ER stress in the alveolar epi... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5659140 Fri, 27 Jan 2012 05:00:00 +0100 5659140 http://www.medworm.com/index.php?rid=5659139&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22287607%26dopt%3DAbstract Authors: Fernandez-Gonzalez A, Mitsialis SA, Liu X, Kourembanas S Abstract Bronchopulmonary dysplasia (BPD) is characterized by simplified alveolarization and arrested vascular development of the lung with associated evidence of endothelial dysfunction, inflammation, increased oxidative damage and iron deposition. Heme oxygenase-1 (HO-1) has been reported to be protective in the pathogenesis of diseases of inflammatory and oxidative etiology. Because HO-1 is involved in the response to oxidative stress produced by hyperoxia and is critical for cellular heme and iron homeostasis, it could play a protective role in BPD. Therefore, we investigated the effect of HO-1 in hyperoxia-induced lung injury using a neonatal transgenic mouse model with constitutive lung-specific HO-1 overexpres... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5659139 Fri, 27 Jan 2012 05:00:00 +0100 5659139 http://www.medworm.com/index.php?rid=5659138&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22287608%26dopt%3DAbstract Conclusions) These results suggest that peroxynitrite can influence tissue remodeling by promoting gelatinases release, while theophylline suppresses peroxynitrite-induced tissue remodeling via pathways involving NF-κB/TGF-β(1) and/or HDAC in the HFL-1 cell line. PMID: 22287608 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5659138 Fri, 27 Jan 2012 05:00:00 +0100 5659138 http://www.medworm.com/index.php?rid=5659137&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22287609%26dopt%3DAbstract Authors: Westover AJ, Hooper SB, Wallace MJ, Moss TJ Abstract Intra-amniotic (IA) lipopolysaccharide (LPS) induces intrauterine and fetal lung inflammation, and increases lung surfactant and compliance in preterm sheep; however, the mechanisms are unknown. Prostaglandins (PGs) are inflammatory mediators and PGE(2) has established roles in fetal lung surfactant production. The aim of our first study was to determine PGE(2) concentrations in response to IA LPS and gene expression for pulmonary PG synthetic (Prostaglandin H Synthase-2 (PGHS-2), PGE synthase (PGES)) and metabolizing (prostaglandin dehydrogenase (PGDH)) enzymes and PGE(2) receptors. Our second study aimed to block LPS-induced increases in PGE(2) with a PGHS-2 inhibitor (nimesulide) and determine lung inflammation and su... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5659137 Fri, 27 Jan 2012 05:00:00 +0100 5659137 http://www.medworm.com/index.php?rid=5659136&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22287610%26dopt%3DAbstract Authors: Christou H, Reslan OM, Mam V, Tanbe AF, Vitali SH, Touma M, Arons E, Mitsialis SA, Kourembanas S, Khalil RA Abstract Pulmonary hypertension (PH) is characterized by pulmonary arteriolar remodeling with excessive pulmonary vascular smooth muscle cell (VSMC) proliferation. This results in decreased responsiveness of the pulmonary circulation to vasodilator therapies. We have shown that extracellular acidosis inhibits VSMC proliferation in vitro. We therefore tested whether induction of non-hypercapnic acidosis in vivo ameliorates PH and the underlying pulmonary vascular remodeling and dysfunction. Adult male Sprague-Dawley rats were exposed to hypoxia (8.5% O(2)) for two weeks, or injected s.c. with monocrotaline (MCT, 60 mg/kg) to develop PH. Acidosis was induced with NH4Cl... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5659136 Fri, 27 Jan 2012 05:00:00 +0100 5659136 http://www.medworm.com/index.php?rid=5659135&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22287611%26dopt%3DAbstract Authors: Dipaolo BC, Margulies SS Abstract Alveolar epithelial cells (AEC) maintain integrity of the blood-gas barrier with actin anchored intercellular tight junctions (TJ). Stretched type I-like AECs undergo magnitude and frequency-dependent actin cytoskeleton remodeling into perijunctional actin rings (PJARs). Based on published studies in human pulmonary artery endothelial cells (HPAEC), we hypothesize RhoA activity, Rho kinase (ROCK) activity, and phosphorylation of myosin light chain II (MLC2) increases in stretched type I-like AECs in a manner that is dependent on stretch magnitude, and that RhoA, ROCK, or MLC2 activity inhibition will attenuate stretch-induced actin remodeling and preserve barrier properties. Primary type I-like AEC monolayers were stretched biaxially to cr... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5659135 Fri, 27 Jan 2012 05:00:00 +0100 5659135 http://www.medworm.com/index.php?rid=5659134&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22287612%26dopt%3DAbstract Authors: Olave N, Nicola T, Zhang W, Bulger A, James ML, Oparil S, Chen YF, Ambalavanan N Abstract We have previously shown that inhibition of transforming growth factor-β (TGF-β) signaling attenuates hypoxia-induced inhibition of alveolar development and abnormal pulmonary vascular remodeling in the newborn mice, and that endothelin-A receptor (ETAR) antagonists prevent and reverse the vascular remodeling. The current study tested the hypothesis that inhibition of TGF-β signaling attenuates ET-1 expression and thereby reduces effects of hypoxia on the newborn lung. C57BL/6 mice were exposed from birth to two weeks of age to either air or hypoxia (12% O(2)) while being given either BQ610 (ETAR antagonist), BQ788 (ETBR antagonist), 1D11 (TGF-β neutralizing antibody), or vehicle.... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5659134 Fri, 27 Jan 2012 05:00:00 +0100 5659134 http://www.medworm.com/index.php?rid=5659133&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22287613%26dopt%3DAbstract Authors: Liang J, Jung Y, Tighe RM, Xie T, Liu N, Leonard M, Gunn MD, Jiang D, Noble PW Abstract CCL2 (MCP-1) expression is upregulated during pulmonary inflammation, and the CCL2-CCR2 axis plays a critical role in leukocyte recruitment and promotion of host defense against infection. The role of CCL2 in mediating macrophage subpopulations in the pathobiology of non-infectious lung injury is unknown. The goal of this study was to examine the role of CCL2 in non-infectious acute lung injury. Our results show that lung-specific over-expression of CCL2 protected mice from bleomycin-induced lung injury, characterized by significantly reduced mortality, reduced neutrophil accumulation, and decreased accumulation of the inflammatory mediators IL-6, CXCL2 (MIP-2), and CXCL1 (KC). There we... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5659133 Fri, 27 Jan 2012 05:00:00 +0100 5659133 http://www.medworm.com/index.php?rid=5659132&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22287614%26dopt%3DAbstract Conclusions: Airways remodeling is a cardinal feature of severe asthma. These results demonstrate that allergen-driven airway remodeling can be inhibited by FTY720, offering potential new therapies for the treatment of severe asthma. PMID: 22287614 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5659132 Fri, 27 Jan 2012 05:00:00 +0100 5659132 http://www.medworm.com/index.php?rid=5623249&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22268116%26dopt%3DAbstract Call for Papers: "Bioengineering the Lung: Molecules, Materials, Matrix, Morphology and Mechanics' Am J Physiol Lung Cell Mol Physiol. 2012 Jan 20; Authors: Prakash YS, Stenmark KR Abstract Not applicable. PMID: 22268116 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5623249 Fri, 20 Jan 2012 05:00:00 +0100 5623249 http://www.medworm.com/index.php?rid=5623248&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22268117%26dopt%3DAbstract Authors: Quinton LJ Abstract N/A. PMID: 22268117 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5623248 Fri, 20 Jan 2012 05:00:00 +0100 5623248 http://www.medworm.com/index.php?rid=5623247&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22268118%26dopt%3DAbstract In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma. PMID: 22268118 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5623247 Fri, 20 Jan 2012 05:00:00 +0100 5623247 http://www.medworm.com/index.php?rid=5623246&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22268119%26dopt%3DAbstract Authors: Shi JX, Su X, Xu J, Zhang WY, Shi Y Abstract Tristetraprolin (TTP), a substrate of p38 mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), is an RNA-binding protein that binds to AU-rich elements (AREs) in the 3'-untranslated region (3'-UTR) of its target mRNAs and accelerates mRNA degradation. A previous study by our group showed that MK2 regulates tumor necrosis factor-α (TNF-α)-induced expression of intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8) in human lung microvascular endothelial cells, however, the downstream protein of MK2 remains unknown. Interestingly, both ICAM-1 and IL-8 have AREs in the 3'-UTR of their mRNAs. In the present study, we performed experiments to determine whether MK2 regulates TNF-α-induced expressio... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5623246 Fri, 20 Jan 2012 05:00:00 +0100 5623246 http://www.medworm.com/index.php?rid=5623245&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22268120%26dopt%3DAbstract This study was conducted to examine the relationship between the peroxisome proliferator-associated receptor (PPAR)γ and MUC1 mucin, two anti-inflammatory molecules expressed in the airways. Treatment of A549 lung epithelial cells or primary mouse tracheal surface epithelial (MTSE) cells with phorbol 12-myristate 13-acetate (PMA) increased the levels of tumor necrosis factor (TNF)-α in cell culture media compared with cells treated with vehicle alone. Overexpression of MUC1 in A549 cells decreased PMA-stimulated TNF-α levels, whereas deficiency of Muc1 expression in MTSE cells from Muc1 null mice increased PMA-induced TNF-α levels. Treatment of A549 or MTSE cells with the PPARγ agonist, troglitazone (TGN), blocked the ability of PMA to stimulate TNF-α levels. However, the effect of T... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5623245 Fri, 20 Jan 2012 05:00:00 +0100 5623245 http://www.medworm.com/index.php?rid=5623244&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22268121%26dopt%3DAbstract Authors: Campos R, Shimizu MH, Volpini RA, de Bragança AC, Andrade LC, Lopes FD, Olivo CR, Canale D, Seguro AC Abstract Sepsis is a common cause of acute kidney injury (AKI) and acute lung injury. Oxidative stress plays as important role in such injury. The aim of this study was to evaluate the effects that the potent antioxidant N-acetylcysteine (NAC) has on renal and pulmonary function in rats with sepsis. Rats, treated or not with NAC (4.8 g/L in drinking water), underwent cecal ligation and puncture (CLP) two days after the initiation of NAC treatment, which was maintained throughout the study. At 24 h post-CLP, renal and pulmonary function were studied in four groups: control, control+NAC, CLP, and CLP+NAC. All animals were submitted to low-tidal-volume mechanical ventilation... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5623244 Fri, 20 Jan 2012 05:00:00 +0100 5623244 http://www.medworm.com/index.php?rid=5623243&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22268122%26dopt%3DAbstract Authors: Ruwanpura SM, McLeod L, Miller A, Jones JE, Vlahos R, Ramm G, Longano A, Bardin PG, Bozinovski S, Anderson GP, Jenkins BJ Abstract Interleukin (IL)-6 is a potent immunomodulatory cytokine that is associated with emphysema, a major component of chronic obstructive pulmonary disease (COPD). IL-6 signaling via the gp130 co-receptor is coupled to multiple signaling pathways, especially the latent transcription factor signal transducer and activator of transcription (Stat)3. However, the pathological role of endogenous gp130-dependent Stat3 activation in emphysema is ill-defined. To elucidate the role of the IL-6/gp130/Stat3 signaling axis in the cellular and molecular pathogenesis of emphysema, we employed a genetic complementation strategy using emphysematous gp130(F/F) mice ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5623243 Fri, 20 Jan 2012 05:00:00 +0100 5623243 http://www.medworm.com/index.php?rid=5623242&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22268123%26dopt%3DAbstract This study provides new evidence for the potential utility of CoQ(1) as a non-destructive indicator of the impact of pharmacological or pathological exposures on complex I activity in the intact perfused mouse lung. PMID: 22268123 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5623242 Fri, 20 Jan 2012 05:00:00 +0100 5623242 http://www.medworm.com/index.php?rid=5623241&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22268124%26dopt%3DAbstract Authors: Richards T, Park C, Chen Y, Gibson KF, Di YP, Pardo A, Watkins SC, Choi AM, Selman M, Pilewski JM, Kaminski N, Zhang Y Abstract Idiopathic pulmonary fibrosis (IPF) is a complex disease with poorly understood etiology. Previously we reported up-regulation of matrix metalloproteinase 7 (MMP7) in both lung and peripheral blood of IPF patients. Here we report evidence for genetic correlation of plasma levels and promoter polymorphisms (rs11568818 and rs11568819) of MMP7 in a well-characterized IPF cohort. Both the AA genotype of rs11568818 and the CT genotype of rs11568819 were found to be significantly associated with higher MMP7 plasma levels. These associations were observed only in IPF patients and not in healthy controls. The G-to-A transition of rs11568818 resulted in a ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5623241 Fri, 20 Jan 2012 05:00:00 +0100 5623241 http://www.medworm.com/index.php?rid=5623240&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22268125%26dopt%3DAbstract Authors: Burnham EL, McCord JM, Bose S, Brown LA, House R, Moss M, Gaydos J Abstract Alcohol use disorders (AUDs), including alcohol abuse and dependence, have been linked to the development of acute lung injury (ALI). Prior clinical investigations suggested an association between AUDs and abnormal alveolar epithelial permeability mediated through pulmonary oxidative stress that may partially explain this relationship. We sought to determine if correcting pulmonary oxidative stress in the setting of AUDs would normalize alveolar epithelial permeability in a double-blinded, randomized, placebo-controlled trial of Protandim, a nutraceutical reported to enhance antioxidant activity. We randomized 30 otherwise healthy AUD subjects to receive directly observed inpatient oral therapy wit... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5623240 Fri, 20 Jan 2012 05:00:00 +0100 5623240 http://www.medworm.com/index.php?rid=5578548&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227203%26dopt%3DAbstract Authors: Schneberger D, Aharonson-Raz K, Singh B Abstract Pulmonary intravascular macrophages (PIMs) are constitutively found in species such as cattle, horse, pig, sheep, goat, cats and whales, and can be induced in species such as rats, which normally lack them. It is believed that human lung lacks PIMs but there are previous suggestions of their induction in patients suffering from liver dysfunction. Recent data show induction of PIMs in bile-duct ligated rats, and humans suffering from hepato-pulmonary syndrome. Because constitutive and induced PIMs are pro-inflammatory in response to endotoxins and bacteria, there is a need to study their biology in inflammatory lung diseases such as sepsis, asthma, chronic obstructive pulmonary diseases or hepato-pulmonary syndrome. We provid... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5578548 Fri, 06 Jan 2012 05:00:00 +0100 5578548 http://www.medworm.com/index.php?rid=5578547&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227204%26dopt%3DAbstract DIRECT AND INDIRECT ROLES FOR B-CATENIN IN FACULTATIVE BASAL PROGENITOR CELL DIFFERENTIATION. Am J Physiol Lung Cell Mol Physiol. 2012 Jan 6; Authors: Smith MK, Koch PJ, Reynolds SD Abstract The conducting airway epithelium is maintained and repaired by endogenous progenitor cells. Dysregulated progenitor cell proliferation and differentiation is thought to contribute to epithelial dysplasia in chronic lung disease. Thus, modification of progenitor cell function is an attractive therapeutic goal and one that would be facilitated by knowledge of the molecular pathways that regulate their behavior. We modeled the human tracheobronchial epithelium using primary mouse tracheal epithelial cell cultures that were differentiated by exposure to the air-liquid-interface (ALI). A bas... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5578547 Fri, 06 Jan 2012 05:00:00 +0100 5578547 http://www.medworm.com/index.php?rid=5578546&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227205%26dopt%3DAbstract Authors: Mir-Kasimov M, Sturrock A, McManus ML, Paine R Abstract Local pulmonary expression of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is critically important for defense of the pulmonary alveolar space. It is required for surfactant homeostasis and pulmonary innate immune responses, and is protective against lung injury and aberrant repair. Alveolar epithelial cells (AEC) are a major source of GM-CSF; however the control of homeostatic expression of GM-CSF is incompletely characterized. Increasing evidence suggests considerable plasticity of expression of AEC phenotypic characteristics. We tested the hypothesis that this plasticity extends to regulation of expression of GM-CSF using 1) MLE-12 cells (a commonly used murine cell line expressing some features of nor... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5578546 Fri, 06 Jan 2012 05:00:00 +0100 5578546 http://www.medworm.com/index.php?rid=5578545&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227206%26dopt%3DAbstract This study establishes that BMPR-II deficiency leads to failed growth suppression by TGF-β(1) in PASMCs. This effect is Smad-independent but is associated with inappropriately altered NF-κB signaling and enhanced induction of IL-6 and IL-8 expression. Our study provides a rationale to test anti-interleukin therapies as an intervention to neutralize this inappropriate response and restore the anti-proliferative response to TGF-β(1). PMID: 22227206 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5578545 Fri, 06 Jan 2012 05:00:00 +0100 5578545 http://www.medworm.com/index.php?rid=5578544&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227207%26dopt%3DAbstract In this study, we found increased expression of miR-21 in distal small arteries in the lungs of hypoxia exposed mice. Putative miR-21 targets, including BMPR2, WWP1, SATB1, and YOD1, were downregulated in the lungs of hypoxia exposed mice and in human pulmonary artery smooth muscle cells (PASMCs) overexpressing miR-21. We found that sequestration of miR-21, either before or after hypoxia exposure, diminished chronic hypoxia induced PH and attenuated hypoxia induced pulmonary vascular remodeling, likely through relieving the suppressed expression of miR-21 targets in the lungs of hypoxia exposed mice. Overexpression of miR-21 enhanced, whereas downregulation of miR-21 diminished the proliferation of human PASMCs in vitro and the expression of cell proliferation associated proteins, such as ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5578544 Fri, 06 Jan 2012 05:00:00 +0100 5578544 http://www.medworm.com/index.php?rid=5550442&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198906%26dopt%3DAbstract Authors: Maloney JP, Stearman RS, Bull TM, Calabrese DW, Tripp-Addison ML, Wick MJ, Broeckel U, Robbins IM, Wheeler LA, Cogan JD, Loyd JE Abstract Most patients with familial pulmonary arterial hypertension (FPAH) carry mutations in the bone morphogenic protein receptor 2 gene (BMPR2). Yet carriers have only a 20% risk of disease, suggesting that other factors influence penetrance. Thrombospondin-1 (TSP1) regulates activation of TGF-β and inhibits endothelial and smooth muscle cell proliferation - pathways coincidentally altered in PAH. To determine if a subset of FPAH patients also have mutations in the TSP1 gene (THBS1) we resequenced the type I repeats of THBS1 encoding the TGF-β regulation and cell growth inhibition domains in 60 FPAH probands, 70 nonfamilial PAH subjects, an... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5550442 Fri, 23 Dec 2011 05:00:00 +0100 5550442 http://www.medworm.com/index.php?rid=5550441&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198907%26dopt%3DAbstract Authors: Baron RM, Choi AJ, Owen CA, Choi AM Abstract Gene targeting in mice (transgenic and knockout) has provided investigators with an unparalleled armamentarium in recent decades to dissect the cellular and molecular basis of critical pathophysiological states. Fruitful information has been derived from studies using these genetically engineered mice with significant impact on our understanding, not only of specific biological processes spanning cell proliferation to cell death, but also of critical molecular events involved in the pathogenesis of human disease. This review will focus on the use of gene-targeted mice to study various models of lung disease including airways diseases such as asthma and chronic obstructive pulmonary disease, and parenchymal lung diseases includin... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5550441 Fri, 23 Dec 2011 05:00:00 +0100 5550441 http://www.medworm.com/index.php?rid=5550440&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198908%26dopt%3DAbstract In this study we determined the effects of the NADPH oxidase inhibitor apocynin on oxygenation, ROS levels and NO signaling in PPHN lambs. PPHN was induced in lambs by antenatal ligation of ductus arteriosus 9d prior to delivery. Lambs were treated with vehicle or 3mg/kg of intratracheal apocynin at birth, then ventilated with 100% O(2) for 24h. A significant improvement in oxygenation was observed in apocynin-treated lambs after 24h of ventilation. Contractility of isolated fifth generation PA to norepinephrine was attenuated in apocynin lambs. PA constrictions to nitric oxide synthase (NOS) inhibition with L-NA were blunted in PPHN lambs; apocynin restored contractility to L-NA, suggesting increased NOS activity. Intratracheal apocynin also enhanced PA relaxations to the endothelial NOS ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5550440 Fri, 23 Dec 2011 05:00:00 +0100 5550440 http://www.medworm.com/index.php?rid=5550439&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198909%26dopt%3DAbstract The objective of this study was to evaluate the effects of hydrocortisone on pulmonary vascular function, ROS, and cGMP in the ovine ductal ligation model of PPHN. PPHN lambs were ventilated with 100% O(2) for 24 hours. Six lambs received 5mg/kg hydrocortisone every 8 hours x 3 doses (PPHN-hiHC), five lambs received 3mg/kg hydrocortisone followed by 1 mg/kg/dose x 2 doses (PPHN-loHC), and six lambs were ventilated with O(2) alone (PPHN). All groups were compared to healthy one-day spontaneously breathing lambs (1DSB). O(2) ventilation of PPHN lambs decreased sGC activity, increased PDE5 activity, and increased ROS vs. 1DSB lambs. Both hydrocortisone doses significantly improved a/A ratios relative to PPHN lambs, decreased PDE5 activity, and increased cGMP relative to PPHN lambs. High-dose ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5550439 Fri, 23 Dec 2011 05:00:00 +0100 5550439 http://www.medworm.com/index.php?rid=5535292&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22180657%26dopt%3DAbstract Authors: Greenwood KK, Proper SP, Saini Y, Bramble LA, Jackson-Humbles DN, Wagner JG, Harkema JR, Lapres JJ Abstract Allergic airway disease is characterized by a T helper type 2 cell-mediated airway inflammation and airway hyperresponsiveness. Little is known about the role of hypoxia-mediated signaling in the progression of the disease. To address this knowledge gap, a mouse model was created in which doxycycline exposure induces the functional deletion of hypoxia inducible factor-1α from alveolar type II and Clara cells of the lung. When hypoxia inducible factor-1α deletion was induced during the early post-natal development period of the lung, the mice display an enhanced response to the ovalbumin model of allergic airway disease. These hypoxia inducible factor-1α-deficient ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5535292 Fri, 16 Dec 2011 05:00:00 +0100 5535292 http://www.medworm.com/index.php?rid=5535291&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22180658%26dopt%3DAbstract Authors: Cho KA, Suh JW, Sohn JH, Park JW, Lee H, Kang JL, Woo SY, Cho YJ Abstract Allergic asthma is characterized by infiltration of eosinophils, elevated Th2 cytokine levels, airway hyper-responsiveness, and IgE. In addition to eosinophils, mast cells, and basophils, a variety of cytokines are also involved in the development of allergic asthma. The pivotal role of eosinophils in the progression of the disease has been a subject of controversy. To determine the role of eosinophils in the progression of airway inflammation, we sensitized and challenged Balb/c wild-type (WT) mice and eosinophil-deficient ΔdblGATA mice with ovalbumin (OVA), and analyzed different aspects of inflammation. We observed increased eosinophil levels and a Th2-dominant response in OVA-challenged WT mice.... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5535291 Fri, 16 Dec 2011 05:00:00 +0100 5535291 http://www.medworm.com/index.php?rid=5535290&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22180659%26dopt%3DAbstract Right Place, Right Time: The evolving role of herpesvirus infection as a "second hit" in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2011 Dec 16; Authors: Kropski JA, Lawson WE, Blackwell TS Abstract Over the course of the past decade, increasing evidence has implicated alveolar epithelial cell injury and dysfunction in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Genetic factors, cigarette smoking, and other environmental exposures have been identified as potential factors leading to a population of vulnerable alveolar epithelial cells. In addition, molecular techniques have demonstrated herpesviruses are commonly detectable in the lungs of patients with IPF, raising suspicion that in the setting of a vulnerable alveolar epithelium, lytic... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5535290 Fri, 16 Dec 2011 05:00:00 +0100 5535290 http://www.medworm.com/index.php?rid=5535289&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22180660%26dopt%3DAbstract Conclusion: Together, these findings suggest that cytoskeletal function is central to the development of BMPR2-associated PAH and that intervention against cytoskeletal defects may reverse established disease. PMID: 22180660 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5535289 Fri, 16 Dec 2011 05:00:00 +0100 5535289 http://www.medworm.com/index.php?rid=5535298&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22160304%26dopt%3DAbstract Authors: Goodson P, Kumar A, Jain L, Kundu K, Murthy N, Koval M, Helms MN Abstract To define roles for reactive oxygen species (ROS) and lung ENaC in maintaining alveolar fluid balance in vivo, we used two novel whole animal imaging approaches. Live X-ray fluoroscopy enabled quantification of airspace fluid content of C57Bl/6 mouse lungs challenged by intratracheal (IT) instillation of saline; results were confirmed using conventional lung wet/dry weight ratios and Evans Blue assay as measures of pulmonary edema. Visualization and quantification of ROS produced in lungs was performed using mice which had been administered a redox sensitive dye, hydrocyanine 7, by IT instillation. We found that that inhibition of NADPH oxidase with a Rac-1 inhibitor, NSC23766, resulted in alveolar f... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5535298 Fri, 09 Dec 2011 05:00:00 +0100 5535298 http://www.medworm.com/index.php?rid=5535297&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22160305%26dopt%3DAbstract Conclusions: Our experiments indicate that PM(2.5) potentiates a pro-inflammatory Th1 response involving increased homing of CXCR3(+) T effector cells to the lung and modulation of systemic T cell populations. PMID: 22160305 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5535297 Fri, 09 Dec 2011 05:00:00 +0100 5535297 http://www.medworm.com/index.php?rid=5535296&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22160306%26dopt%3DAbstract Authors: Kuypers E, Collins JJ, Kramer BW, Ofman G, Nitsos I, Pillow JJ, Polglase GR, Kemp MW, Newnham JP, Gavilanes AW, Nowacki R, Ikegami M, Jobe AH, Kallapur SG Abstract The proinflammatory stimulus of chorioamnionitis is commonly associated with preterm delivery. Women at risk of preterm delivery receive antenatal glucocorticoids to functionally mature the fetal lung. However, the effects of the combined exposures of chorioamnionitis and antenatal glucocorticoids on the fetus are poorly understood. Time-mated ewes with singleton fetuses received an intra-amniotic injection of lipopolysaccharide (LPS) either preceding or following maternal intra-muscular betamethasone 7 or 14 days before delivery, and the fetuses were delivered at 120 days gestational age (GA) (term=150 days GA)... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5535296 Fri, 09 Dec 2011 05:00:00 +0100 5535296 http://www.medworm.com/index.php?rid=5535295&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22160307%26dopt%3DAbstract Conclusions: This is the first study to demonstrate a role for the glycocalyx in whole lung mechano-transduction and has important implications in understanding the regulation of vascular permeability in the context of vascular pressure, fluid status and ventilation strategies. PMID: 22160307 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5535295 Fri, 09 Dec 2011 05:00:00 +0100 5535295 http://www.medworm.com/index.php?rid=5535294&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22160308%26dopt%3DAbstract Authors: Ghavami S, Mutawe MM, Schaafsma D, Yeganeh B, Unruh H, Klonisch T, Halayko AJ Abstract Geranylgeranyl transferase 1 (GGT1) is involved in the posttranslational prenylation of signaling proteins, such as small GTPases. We have shown that blocking the formation of isoprenoids with statins regulates survival of human lung mesenchymal cells, thus we tested the hypothesis that GGT1 may specifically modulate programmed cell death pathways in these cells. To this end, human airway smooth muscle cells (HASM) were treated with the selective GGT1 inhibitor, GGTi-298. Apoptosis was seen using assays for cellular DNA content and caspase activation. Induction of autophagy was observed using transmission electron microscopy, immunoblotting for LC3 lipidation and Atg5-12 complex content,... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5535294 Fri, 09 Dec 2011 05:00:00 +0100 5535294 http://www.medworm.com/index.php?rid=5535293&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22160309%26dopt%3DAbstract In this study, experiments were performed to evaluate the role of TLR4 in pulmonary responses against Klebsiella pneumoniae (Kp). As compared to WT (Balb/c) mice, mice with defective TLR4 signaling (TLR4(lps-d) mice) had substantially higher lung bacterial CFU after i.t. challenge with Kp, which was associated with considerably greater lung permeability and lung cell death. Reduced expression of GM-CSF mRNA and protein was noted in lungs and bronchoalveolar lavage fluid (BALF) of TLR4 mutant mice post i.t. Kp, as compared to WT mice, and primary alveolar epithelial cells (AEC) harvested from TLR4(lps-d) mice produced significantly less GM-CSF in-vitro in response to heat-killed Kp as compared to WT AEC. TLR4(lps-d) AEC underwent significantly more apoptosis in response to heat killed Kp in... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5535293 Fri, 09 Dec 2011 05:00:00 +0100 5535293 http://www.medworm.com/index.php?rid=5535302&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22140070%26dopt%3DAbstract Authors: Liu D, Yan Z, Minshall RD, Schwartz DE, Chen Y, Hu G Abstract Lung inflammatory responses in the absence of infection are considered to be one of primary mechanisms of ventilator-induced lung injury. Here, we determined the role of calpain in the pathogenesis of lung inflammation due to mechanical ventilation. Male C57BL/6J mice were subjected to high (28 ml/kg) tidal volume ventilation for 2 h in the absence and presence of calpain inhibitor I (10 mg/kg). To address the isoform specific functions of calpain 1 and calpain 2 during mechanical ventilation, we utilized a liposome-based delivery system to introduce small interfering RNAs (siRNAs) targeting each isoform in pulmonary vasculature in vivo. Mechanical ventilation with high tidal volume induced rapid (within minutes... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5535302 Fri, 02 Dec 2011 05:00:00 +0100 5535302 http://www.medworm.com/index.php?rid=5535301&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22140071%26dopt%3DAbstract Authors: Sturrock A, Seedahmed E, Mir-Kasimov M, Boltax J, McManus ML, Paine R Abstract Exposure of mice to hyperoxia induces alveolar epithelial cell (AEC) injury, acute lung injury and death. Overexpression of GM-CSF in the lung protects against these effects, although the mechanisms are not yet clear. Hyperoxia induces cellular injury via effects on mitochondrial integrity, associated with induction of proapoptotic members of the Bcl-2 family. We hypothesized that GM-CSF protects AEC through effects on mitochondrial integrity. MLE-12 cells (a murine type II cell line) and primary murine type II AEC were subjected to oxidative stress by exposure to 80% oxygen and by exposure to H2O2. Exposure to H2O2 induced cytochrome c release and decreased mitochondrial reductase activity in M... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5535301 Fri, 02 Dec 2011 05:00:00 +0100 5535301 http://www.medworm.com/index.php?rid=5535300&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22140072%26dopt%3DAbstract Authors: Bhandary YP, Shetty SK, Marudamuthu AS, Gyetko MR, Idell S, Gharaee-Kermani M, Shetty RS, Starcher BC, Shetty S Abstract Alveolar type (AT) II cell apoptosis and depressed fibrinolysis that promotes alveolar fibrin deposition is associated with acute lung injury (ALI) and the development of pulmonary fibrosis (PF). We therefore sought to determine if p53-mediated inhibition of urokinase type plasminogen activator (uPA) and induction of plasminogen activator inhibitor-1 (PAI-1) contribute to ATII cell apoptosis that precedes the development of PF. We also sought to determine if caveolin-1 scaffolding domain peptide (CSP) reverses these changes to protect against ALI and PF. Tissues as well as isolated ATII cells from the lungs of wild-type (WT) mice with BLM injury show inc... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5535300 Fri, 02 Dec 2011 05:00:00 +0100 5535300 http://www.medworm.com/index.php?rid=5535299&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22142987%26dopt%3DAbstract Authors: PMID: 22142987 [PubMed - in process] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5535299 Thu, 01 Dec 2011 05:00:00 +0100 5535299 http://www.medworm.com/index.php?rid=5421643&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22080750%26dopt%3DAbstract In conclusion, PGE(2) enhances IL-8 production via EP4 receptor coupled to G(s) protein in HPMVECs. Activation of the cAMP/PKA pathway, followed by p38 activation, is essential for these mechanisms. Because neutrophils play a critical role in the inflammation of ALI/ARDS, IL-8 released from the pulmonary microvasculature in response to PGE(2) may contribute to pathophysiology of this disease. PMID: 22080750 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5421643 Fri, 11 Nov 2011 05:00:00 +0100 5421643 http://www.medworm.com/index.php?rid=5421642&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22080751%26dopt%3DAbstract AJP-Lung: "The best place to publish basic, translational and hypothesis-driven clinical lung research" Am J Physiol Lung Cell Mol Physiol. 2011 Nov 11; Authors: Matalon S Abstract No abstract necessary. PMID: 22080751 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5421642 Fri, 11 Nov 2011 05:00:00 +0100 5421642 http://www.medworm.com/index.php?rid=5421641&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22080752%26dopt%3DAbstract The objective was to study aerobic glycolysis in human asthma and the role of this metabolic pathway in airway hyperreactivity and inflammation in a mouse model of asthma. Human peripheral blood and mouse spleen CD4 T cells were isolated by negative selection. T cell proliferation was measured by thymidine incorporation. Cytokines and serum lactate were measured by ELISA. Mouse airway hyperreactivity to inhaled methacholine was measured by a Flexivent apparatus. The serum lactate concentration was significantly elevated in clinically stable asthmatic subjects as compared to healthy and COPD controls, and negatively correlated with FEV1. Proliferating CD4 T cells from human asthma and a mouse model of asthma produced higher amounts of lactate upon stimulation suggesting a heightened glycoly... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5421641 Fri, 11 Nov 2011 05:00:00 +0100 5421641 http://www.medworm.com/index.php?rid=5380064&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22037357%26dopt%3DAbstract This report tests the hypothesis that the hydrophobic surfactant protein (SP-B) also inhibits sPLA(2)-mediated surfactant hydrolysis. Three surfactant preparations were used containing varied amounts of SP-B and radiolabeled tracers of phosphatidylcholine (PC) or phosphatidylglycerol (PG): (1) washed ovine surfactant (OS) (pre and post organic extraction) compared to Survanta(®), (protein poor), (2) Survanta(®) supplemented with purified bovine SP-B (1-5%, w/w), and 3) a mixture of dipalmitoylphosphatidylcholine (DPPC), 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG) (DPPC:POPC:POPG, 40:40:20) prepared as vesicles and monomolecular films in the presence or absence of SP-B. Hydrolysis of PG and PC by Group IB sPLA(2) (PLA2G1A) was signi... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5380064 Fri, 28 Oct 2011 04:00:00 +0100 5380064 http://www.medworm.com/index.php?rid=5380063&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22037358%26dopt%3DAbstract Authors: Mihai C, Bao S, Lai JP, Ghadiali SN, Knoell DL Abstract The phosphoinositide-3 kinase (PI3K)/Akt pathway is a vital survival axis in lung epithelia. We previously reported that inhibition of PTEN, a major suppressor of this pathway, results in enhanced wound repair following injury. However, the precise cellular and biomechanical mechanisms responsible for increased wound repair during PTEN inhibition are not yet well established. Using primary human lung epithelia and a related lung epithelial cell line, we first determined whether changes in migration or proliferation account for wound closure. Strikingly, we observed that cell migration accounts for the majority of wound recovery following PTEN inhibition in conjunction with activation of the Akt and ERK signaling pathw... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5380063 Fri, 28 Oct 2011 04:00:00 +0100 5380063 http://www.medworm.com/index.php?rid=5380062&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22037359%26dopt%3DAbstract In this study we characterized CEACAM6 expression in vivo in human lung. CEACAM6 was present in lung lavage of premature infants at birth and increased progressively in intubated infants with lung disease. Of surfactant-associated CEACAM6, ~80% was the fully glycosylated, 90 kDa form that contains the GPI anchor, and the concentration (3.9% of phospholipid for adult lung) was comparable to that for surfactant proteins A/B/C. We examined the affinity of CEACAM6 by purification of surfactant on density gradient centrifugation; concentrations of CEACAM6 and SP-B per phospholipid were unchanged whereas levels of total protein and SP-A decreased by 60%. CEACAM6 mRNA content decreased progressively from upper trachea to peripheral fetal lung, whereas protein levels were similar in all regions of... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5380062 Fri, 28 Oct 2011 04:00:00 +0100 5380062 http://www.medworm.com/index.php?rid=5329282&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003086%26dopt%3DAbstract Authors: Wu ZX, Benders KB, Hunter DD, Dey RD Abstract Our recent study showed that prenatal and early postnatal exposure of mice to SS, a surrogate to environmental tobacco smoke (ETS), leads to increased airway responsiveness and sensory innervation later in life. However, the underlying mechanism initiated in early life that affects airway responses later in life remains undefined. The concomitant increase in nerve growth factor (NGF) after exposures suggests that NGF may be involved the regulation of airway innervation. Since NGF regulates sympathetic nerve responses, as well as sensory nerves, we extended previous studies by examining neuropeptide Y (NPY), a neuropeptide associated with sympathetic nerves. Different age groups of mice, postnatal day (PD) 2 and PD21, were expos... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5329282 Fri, 14 Oct 2011 04:00:00 +0100 5329282 http://www.medworm.com/index.php?rid=5329281&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003087%26dopt%3DAbstract Conclusion: TGF-β(1) induced perlecan deposition may enhance attachment of migrating ASMC in vivo and thus may be a mechanism for ASMC layer hypertrophy in COPD. PMID: 22003087 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5329281 Fri, 14 Oct 2011 04:00:00 +0100 5329281 http://www.medworm.com/index.php?rid=5329280&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003088%26dopt%3DAbstract Authors: Manni ML, Epperly MW, Han W, Blackwell TS, Duncan SR, Piganelli JD, Oury TD Abstract The antioxidant enzyme extracellular superoxide dismutase (EC-SOD) is abundant in the lung and is known to limit inflammation and fibrosis following numerous pulmonary insults. Previous studies have reported a loss of full-length EC-SOD from the pulmonary parenchyma with accumulation of proteolyzed EC-SOD in the airspace after an interstitial lung injury. However, following airspace only inflammation, EC-SOD accumulates in the airspace without a loss from the interstitium suggesting this antioxidant may be released from an extrapulmonary source. Since leukocytes are known to express EC-SOD and are prevalent in the bronchoalveolar lavage fluid (BALF) after injury, it was hypothesized that t... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5329280 Fri, 14 Oct 2011 04:00:00 +0100 5329280 http://www.medworm.com/index.php?rid=5329279&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003089%26dopt%3DAbstract Authors: Tang JR, Karumanchi SA, Seedorf GJ, Markham NE, Abman SH Abstract Epidemiologic studies have shown that maternal preeclampsia (PE) increases the risk of bronchopulmonary dysplasia (BPD) but the underlying mechanism is unknown. Soluble vascular endothelial growth factor receptor-1 (soluble VEGFR1, known as soluble fms-like tyrosine kinase 1, or sFlt-1), an endogenous inhibitor of VEGF, is markedly elevated in amniotic fluid and maternal blood in PE. Therefore, we hypothesized that antenatal exposure to excess sFlt-1 disrupts lung development through impaired VEGF signaling in utero, providing a mechanistic link between PE and BPD. To determine whether increased sFlt-1 in amniotic fluid is sufficient to cause sustained abnormalities of lung structure during infancy, sFlt-1 o... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5329279 Fri, 14 Oct 2011 04:00:00 +0100 5329279 http://www.medworm.com/index.php?rid=5329278&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003090%26dopt%3DAbstract Authors: Sutherland KM, Edwards PC, Combs TJ, Van Winkle LS Abstract Exposure to air pollution has been linked to pulmonary diseases. Naphthalene (NA), an abundant polycyclic aromatic hydrocarbon in tobacco smoke and urban air, is a model toxicant for air pollution effects in the lung. Repeated exposures to NA in male mice result in tolerance; defined as the emergence of a resistant cell phenotype after prior exposure. Tolerance has not been studied in females. Females have sex differences in airway epithelial responses and in the prevalence of certain airway diseases. Male and female mice were exposed to a tolerance-inducing regimen of NA and lungs were examined by airway level to characterize the cellular changes associated with repeated NA exposure and to assess the expression o... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5329278 Fri, 14 Oct 2011 04:00:00 +0100 5329278 http://www.medworm.com/index.php?rid=5329277&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003091%26dopt%3DAbstract Authors: Ohta H, Chiba S, Ebina M, Furuse M, Nukiwa T Abstract The dysfunction of alveolar barriers is a critical factor in the development of lung injury and subsequent fibrosis, but the underlying molecular mechanisms remain poorly understood. To clarify the pathogenic roles of tight junctions in lung injury and fibrosis, we examined the altered expression of claudins, the major components of tight junctions, in the lungs of disease models with pulmonary fibrosis. Among the 24 known claudins, claudin-1, claudin-3, claudin-4, claudin-7, and claudin-10 were identified as components of airway tight junctions. Claudin-5 and claudin-18 were identified as components of alveolar tight junctions and were expressed in endothelial and alveolar epithelial cells, respectively. In experimenta... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5329277 Fri, 14 Oct 2011 04:00:00 +0100 5329277 http://www.medworm.com/index.php?rid=5329276&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003092%26dopt%3DAbstract Authors: Deppong CM, Xu J, Brody SL, Green JM Abstract Organ-specific regulation of immune responses relies upon the exchange of information between non-immune and immune cells. In a primary culture model of the lung airway, we demonstrate that T cell proliferation is potently inhibited by airway epithelial cells. This is mediated by activation of the IFNγ/STAT1 pathway in the epithelial cell and TGFβ-dependent suppression of T cell proliferation. In this way, the epithelial cell can restrict the expansion of T cells. Given the constant exposure of the airway to inhaled antigen, this may be important in setting a threshold for the initiation of T dependent immune responses and preventing unwanted, chronic inflammation. PMID: 22003092 [PubMed - as supplied by publisher] (Sourc... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5329276 Fri, 14 Oct 2011 04:00:00 +0100 5329276 http://www.medworm.com/index.php?rid=5329275&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003093%26dopt%3DAbstract Authors: Grubb BR, O'Neal WK, Ostrowski LE, Kreda SM, Button B, Boucher RC Abstract The relationships between the balance of airway epithelial Cl(-) secretion vs. Na(+) absorption, airway surface liquid (ASL) homeostasis, and lung disease were investigated in selected transgenic (Tg) mice. First, to determine if Tg overexpression of wild-type (WT) human CFTR (hCFTR) accelerated Cl(-) secretion and regulated Na(+) absorption in murine airways, we generated mice expressing airway-specific hCFTR, utilizing a Clara cell-specific (CCSP) promoter. Ussing chamber studies revealed that CCSP-hCFTR Tg mouse airways exhibited significantly (~2.5 fold) elevated basal Cl(-) secretory currents. Endogenous murine airway Na(+) absorption was not regulated by hCFTR, and these mice exhibited no lung... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5329275 Fri, 14 Oct 2011 04:00:00 +0100 5329275 http://www.medworm.com/index.php?rid=5329274&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003094%26dopt%3DAbstract Authors: Hou YC, Chiu WC, Yeh CL, Yeh SL Abstract Lung epithelial cells are important barriers in the respiratory system which provoke inflammatory responses through nuclear factor (NF)-κB activation to prevent pathogens from invading the body. Lipopolysaccharide (LPS) is a common pathogen-associated stimulus which activates IκB kinase (IKK) to regulate NF-κB-mediated inflammation through modulating nuclear translocation and phosphorylation of NF-κB. Previously, it was shown that Akt and the mammalian target of rapamycin (mTOR) are involved in the phosphorylation of IKK to activate NF-κB. Herein, we demonstrate that glutamine (GLN) modulated LPS-induced activation of NF-κB through the Akt/mTOR/IKK pathway in BEAS-2B cells. BEAS-2B cells in submerged culture were placed in med... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5329274 Fri, 14 Oct 2011 04:00:00 +0100 5329274 http://www.medworm.com/index.php?rid=5329273&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003095%26dopt%3DAbstract Authors: Vohra PK, Hoeppner LH, Sagar G, Dutta SK, Misra S, Hubmayr RD, Mukhopadhyay D Abstract The neurotransmitter dopamine and its dopamine receptor D2 (D2DR) agonists are known to inhibit vascular permeability factor/vascular endothelial growth factor (VPF/VEGF)-mediated angiogenesis and vascular permeability. Lung injury is a clinical syndrome associated with signs of increased microvascular permeability. However, the effects of dopamine on pulmonary edema, a phenomenon critical to the pathophysiology of both acute and chronic lung injuries, have yet to be established. Therefore, we sought to determine the potential therapeutic effects of dopamine in a murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Compared with sham-treated controls, pre-treatment w... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5329273 Fri, 14 Oct 2011 04:00:00 +0100 5329273 http://www.medworm.com/index.php?rid=5329272&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22003096%26dopt%3DAbstract In conclusion, the present study is the first to demonstrate that diaphragm muscle atrophy resulting from acute pulmonary inflammation requires NF-κB activation and UPS-mediated protein degradation. PMID: 22003096 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5329272 Fri, 14 Oct 2011 04:00:00 +0100 5329272 http://www.medworm.com/index.php?rid=5329287&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21984567%26dopt%3DAbstract In this study, we found that only 6 hours of exposure to CS impaired endothelial barrier function in vivo, an effect associated with increased oxidative stress in the lungs and attenuated by the antioxidant, N-acetylcysteine (NAC). CS also exacerbated lipopolysaccharide (LPS)-induced increase in vascular permeability in vivo. Similar additive effect was also seen in cultured lung EC exposed to cigarette smoke extract (CSE) and LPS. We further demonstrated that CSE caused disruption of focal adhesion complexes (FAC), F-actin fibers and adherens junctions (AJ), and decreased activities of RhoA and focal adhesion kinase (FAK) in cultured lung EC. CSE-induced inhibition of RhoA and FAK, endothelial barrier dysfunction, and disassembly of FAC, F-actin, and AJ were prevented by NAC. In addition,... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5329287 Fri, 07 Oct 2011 04:00:00 +0100 5329287 http://www.medworm.com/index.php?rid=5329286&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21984568%26dopt%3DAbstract Authors: Konsavage WM, Zhang L, Wu Y, Shenberger JS Abstract Diverse environmental stresses stimulate eukaryotic translation initiation factor 2α (eIF2α) phosphorylation leading to a stress-resistant state characterized by global attenuation of protein synthesis and induction of cytoprotective genes. The signal transduction network culminating in these effects is referred to as the integrated stress response (ISR), or when initiated by misfolded proteins within the endoplasmic reticulum, the unfolded protein response (UPR). Given that we previously reported that exposure of 4-day-old Sprague Dawley rats rats to 95% O(2) (Ox) diminishes global pulmonary protein synthesis and increases eIF2α phosphorylation, we conducted the current study to determine if Ox activates the ISR or UP... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5329286 Fri, 07 Oct 2011 04:00:00 +0100 5329286 http://www.medworm.com/index.php?rid=5329285&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21984569%26dopt%3DAbstract Authors: Sharma J, Young DM, Marentette JO, Rastogi P, Turk J, McHowat J Abstract An early event in the pathogenesis of emphysema is the development of inflammation associated with accumulation of polymorphonuclear leukocytes (PMN) in small airways, and inflammatory cell recruitment from the circulation involves migration across endothelial and epithelial cell barriers. Platelet-activating factor (PAF) promotes transendothelial migration in several vascular beds and we postulated that increased PAF production in the airways of smokers might enhance inflammatory cell recruitment and exacerbate inflammation. To examine this possibility, we incubated human lung microvascular endothelial cells (HMVEC-L) with cigarette smoke extract (CSE) and found that CSE inhibits PAF-acetylhydrolase ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5329285 Fri, 07 Oct 2011 04:00:00 +0100 5329285 http://www.medworm.com/index.php?rid=5329284&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21984570%26dopt%3DAbstract Authors: Cyphert JM, Allen IC, Church RJ, Latour AM, Snouwaert JN, Coffman TM, Koller BH Abstract Actions of thromboxane (TXA(2)) to alter airway resistance were first identified over 25 years ago. However, the mechanism underlying this physiological response has remained largely undefined. Here we address this question using a novel panel of mice in which expression of the thromboxane receptor (TP) has been genetically manipulated. We show that the response of the airways to TXA(2) is complex: it depends on expression of other G protein-coupled receptors, but also on the physiological context of the signal. In the healthy airway, TXA(2)-mediated airway constriction depends on expression of TP receptors by smooth muscle cells. In contrast, in the inflamed lung, the direct actions o... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5329284 Fri, 07 Oct 2011 04:00:00 +0100 5329284 http://www.medworm.com/index.php?rid=5329283&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21984571%26dopt%3DAbstract Authors: Ikonomou L, Hemnes AR, Bilousova G, Hamid R, Loyd JE, Hatzopoulos AK, Kotton DN, Majka SM, Austin ED Abstract Human lung research has made remarkable progress over the last century largely due to the use of animal models of disease. The challenge for the future is to translate these findings into human disease and bring about meaningful disease modification or even cure. The ability to generate transformative therapies in the future will require human tissue, currently scarce under the best of circumstances. Unfortunately, patient-derived somatic cells are often poorly characterized and have a limited life span in culture. Moreover, these cells are frequently obtained from patients with end-stage disease exposed to multiple drug therapies, leaving researchers with question... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5329283 Fri, 07 Oct 2011 04:00:00 +0100 5329283 http://www.medworm.com/index.php?rid=5281396&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21724857%26dopt%3DAbstract This study presents an assay useful to distinguish preclinical compounds by a crucial mechanism underlying CFTR activation, delineates two types of compound able to acutely augment CFTR activity (e.g., activators and potentiators), and demonstrates that a number of different mechanisms can be successfully employed to activate mutant CFTR. PMID: 21724857 [PubMed - in process] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281396 Sat, 01 Oct 2011 04:00:00 +0100 5281396 http://www.medworm.com/index.php?rid=5281395&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21724858%26dopt%3DAbstract We examined epithelial repair during cyclic stretch (CS) in a scratch-wound model of primary rat alveolar type II (ATII) cells and found that CS altered the balance between proliferation and cell death. We measured cell migration, size, and density; intercellular gap formation; cell number, proliferation, and apoptosis; cytoskeletal organization; and focal adhesions in response to scratch wounding followed by CS for up to 24 h. Under static conditions, wounds were closed by 24 h, but repair was inhibited by CS. Wounding stimulated cell motility and proliferation, actin and vinculin redistribution, and focal adhesion formation at the wound edge, while CS impeded cell spreading, initiated apoptosis, stimulated cytoskeletal reorganization, and attenuated focal adhesion formation. CS also caus... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281395 Sat, 01 Oct 2011 04:00:00 +0100 5281395 http://www.medworm.com/index.php?rid=5281394&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21724859%26dopt%3DAbstract Authors: Finkbeiner WE, Zlock LT, Morikawa M, Lao AY, Dasari V, Widdicombe JH Abstract -We investigated how cystic fibrosis (CF) alters the relationship between Cl(-) and mucin secretion in cultures of non-CF and CF human tracheobronchial gland mucous (HTGM and CFTGM, respectively) cells. Biochemical studies showed that HTMG cells secreted typical airway mucins, and immunohistochemical studies showed that these cells expressed MUC1, MUC4, MUC5B, MUC8, MUC13, MUC16, and MUC20. Effects of cumulative doses of methacholine (MCh), phenylephrine (Phe), isoproterenol (Iso), and ATP on mucin and Cl(-) secretion were studied on HTGM and CFTGM cultures. Baseline mucin secretion was not significantly altered in CFTGM cells, and the increases in mucin secretion induced by mediators were unalte... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281394 Sat, 01 Oct 2011 04:00:00 +0100 5281394 http://www.medworm.com/index.php?rid=5281393&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21724861%26dopt%3DAbstract Authors: Schmiedl A, Behrens J, Zscheppang K, Purevdorj E, von Mayersbach D, Liese A, Dammann CE Abstract Pulmonary ErbB4 deletion leads to a delay in fetal lung development, alveolar simplification, and lung function disturbances in adult mice. We generated a model of intrauterine infection in ErbB4 transgenic mice to study the additive effects of antenatal LPS administration and ErbB4 deletion during fetal lung development. Pregnant mice were treated intra-amniotically with an LPS dose of 4 μg at E17 of gestation. Lungs were analyzed 24 h later. A significant influx of inflammatory cells was seen in all LPS-treated lungs. In heterozygote control lungs, LPS treatment resulted in a delay of lung morphogenesis characterized by a significant increase in the fraction of mesenchyme, a... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281393 Sat, 01 Oct 2011 04:00:00 +0100 5281393 http://www.medworm.com/index.php?rid=5281392&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21743024%26dopt%3DAbstract Authors: Farkas L, Farkas D, Warburton D, Gauldie J, Shi W, Stampfli MR, Voelkel NF, Kolb M Abstract The concept of genetic susceptibility factors predisposing cigarette smokers to develop emphysema stems from the clinical observation that only a fraction of smokers develop clinically significant chronic obstructive pulmonary disease. We investigated whether Smad3 knockout mice, which develop spontaneous air space enlargement after birth because of a defect in transforming growth factor-β (TGF-β) signaling, develop enhanced alveolar cell apoptosis and air space enlargement following cigarette smoke exposure. We investigated Smad3(-/-) and Smad3(+/+) mice at different adult ages and determined air space enlargement, alveolar cell proliferation, and apoptosis. Furthermore, laser-ca... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281392 Sat, 01 Oct 2011 04:00:00 +0100 5281392 http://www.medworm.com/index.php?rid=5281391&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21743026%26dopt%3DAbstract Authors: Wright C, Pilkington R, Callaghan M, McClean S Abstract Burkholderia cepacia complex is a group of bacterial pathogens that cause opportunistic infections in cystic fibrosis (CF). The most virulent of these is Burkholderia cenocepacia. Matrix metalloproteinases (MMPs) are upregulated in CF patients. The aim of this work was to examine the role of MMPs in the pathogenesis of B. cepacia complex, which has not been explored to date. Real-time PCR analysis showed that B. cenocepacia infection upregulated MMP-2 and MMP-9 genes in the CF lung cell line CFBE41o- within 1 h, whereas MMP-2, -7, and -9 genes were upregulated in the non-CF lung cell line 16HBE14o-. Conditioned media from both cell lines showed increased MMP-9 activation following B. cenocepacia infection. Conditioned... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281391 Sat, 01 Oct 2011 04:00:00 +0100 5281391 http://www.medworm.com/index.php?rid=5281390&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21743030%26dopt%3DAbstract Authors: Redente EF, Jacobsen KM, Solomon JJ, Lara AR, Faubel S, Keith RC, Henson PM, Downey GP, Riches DW Abstract Fibrotic interstitial pneumonias are more prevalent in males of advancing age, although little is known about the underlying mechanisms. To evaluate the contributions of age and sex to the development of pulmonary fibrosis, we intratracheally instilled young (8-12 wk) and aged (52-54 wk) male and female mice with bleomycin and assessed the development and severity of fibrotic lung disease by measurements of lung collagen levels, static compliance, leukocyte infiltration, and stereological quantification of fibrotic areas in histological sections. We also quantified proinflammatory and profibrotic chemokine and cytokine levels in the bronchoalveolar lavage fluid. Aged ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281390 Sat, 01 Oct 2011 04:00:00 +0100 5281390 http://www.medworm.com/index.php?rid=5281389&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21743031%26dopt%3DAbstract In conclusion, VILI can be reverted by normalizing ventilation pressures. An adequate inflammatory response and extracellular matrix remodeling are essential for recovery. MMP-2 could play a key role in epithelial repair after VILI and acute respiratory distress syndrome. PMID: 21743031 [PubMed - in process] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281389 Sat, 01 Oct 2011 04:00:00 +0100 5281389 http://www.medworm.com/index.php?rid=5281388&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21784968%26dopt%3DAbstract Authors: Wang Y, Voelker DR, Lugogo NL, Wang G, Floros J, Ingram JL, Chu HW, Church TD, Kandasamy P, Fertel D, Wright JR, Kraft M Abstract Surfactant protein A (SP-A) regulates a variety of immune cell functions. We determined the ability of SP-A derived from normal and asthmatic subjects to modulate the inflammatory response elicited by Mycoplasma pneumoniae, a pathogen known to exacerbate asthma. Fourteen asthmatic and 10 normal control subjects underwent bronchoscopy with airway brushing and bronchoalveolar lavage (BAL). Total SP-A was extracted from BAL. The ratio of SP-A1 to total SP-A (SP-A1/SP-A) and the binding of total SP-A to M. pneumoniae membranes were determined. Airway epithelial cells from subjects were exposed to either normal or asthmatic SP-A before exposure to M.... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281388 Sat, 01 Oct 2011 04:00:00 +0100 5281388 http://www.medworm.com/index.php?rid=5281387&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21784970%26dopt%3DAbstract In this study, we identified functionally important transcription factor binding sites in the TTF-1 proximal promoter and studied tumor necrosis factor-α (TNF-α) regulation of TTF-1 expression. TNF-α, a proinflammatory cytokine, has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) and inhibits surfactant protein levels. Deletion analysis of TTF-1 5'-flanking DNA indicated that the TTF-1 proximal promoter retained high-level activity. Electrophoretic mobility shift assay, chromatin immunoprecipitation, and mutational analysis experiments identified functional ZBP-89, Sp1, Sp3, and TTF-1 sites in the TTF-1 proximal promoter. TNF-α inhibited TTF-1 protein levels in H441 and primary alveolar type II cells. TNF-α inhibited TTF-1 gene transcription and promo... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281387 Sat, 01 Oct 2011 04:00:00 +0100 5281387 http://www.medworm.com/index.php?rid=5281386&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803868%26dopt%3DAbstract This study identifies an alternative pathway to paracrine signaling to convey regulatory signals from PAECs to PASMCs and raises the possibility that dysregulation of this direct interaction is involved in the pathogenesis of hypertensive pulmonary vascular remodeling. PMID: 21803868 [PubMed - in process] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281386 Sat, 01 Oct 2011 04:00:00 +0100 5281386 http://www.medworm.com/index.php?rid=5281385&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21856812%26dopt%3DAbstract Authors: Pitt BR, Christman JW, Gunst SJ, Matthay MA, Stevens T, Ware LB PMID: 21856812 [PubMed - in process] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281385 Sat, 01 Oct 2011 04:00:00 +0100 5281385 http://www.medworm.com/index.php?rid=5281401&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21949154%26dopt%3DAbstract In conclusion: PDE4 inhibition attenuated and partially reversed PH and RVH, but did not advance alveolar development in neonatal rats with hyperoxic lung injury or affect normal lung and heart development. PMID: 21949154 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281401 Fri, 23 Sep 2011 04:00:00 +0100 5281401 http://www.medworm.com/index.php?rid=5281400&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21949155%26dopt%3DAbstract In this study we hypothesized that hyperoxia affects expression of Trek-1 in alveolar epithelial cells and that Trek-1 is involved in regulation of cell proliferation and cytokine secretion. We found gene expression of several K2P channels in mouse alveolar epithelial cells (MLE-12), and expression of Trek-1 was significantly downregulated in cultured cells and lungs of mice exposed to hyperoxia. Similarly, Proliferation Cell Nuclear Antigen (PCNA) and Cyclin D1 expression were downregulated by exposure to hyperoxia. We developed an MLE-12 cell line deficient in Trek-1 expression using shRNA and found that Trek-1 deficiency resulted in increased cell proliferation and upregulation of PCNA but not Cyclin D1. Furthermore, IL-6 and RANTES secretion was decreased in Trek-1 deficient cells whil... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281400 Fri, 23 Sep 2011 04:00:00 +0100 5281400 http://www.medworm.com/index.php?rid=5281399&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21949156%26dopt%3DAbstract Conclusion: Selective subunit targeting of endogenous airway smooth muscle-specific GABA(A) receptors may represent a novel therapeutic option for patients in severe bronchospasm. PMID: 21949156 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281399 Fri, 23 Sep 2011 04:00:00 +0100 5281399 http://www.medworm.com/index.php?rid=5281398&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21949157%26dopt%3DAbstract This study tested the hypothesis that endovanilloids produced following LPS treatment activate TRPV1 and cause endoplasmic reticulum (ER) stress/GADD153 expression in lung cells, representing a mechanistic component of lung injury. The TRPV1 agonist nonivamide induced GADD153 expression and caused cytotoxicity in immortalized and primary human bronchial, bronchiolar/alveolar, and microvascular endothelial cells, proportional to TRPV1 mRNA expression. In CF-1 mice, Trpv1 mRNA was most abundant in the alveoli and intratracheal nonivamide treatment promoted Gadd153 expression in the alveolar region. Treatment of CF-1 mice with lipopolysaccharides (LPS) increased Gadd153 in the lung, lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, and lung wet-to-dry weight ratio. Co-treatin... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281398 Fri, 23 Sep 2011 04:00:00 +0100 5281398 http://www.medworm.com/index.php?rid=5281397&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21949158%26dopt%3DAbstract Authors: Soukup B, Benjamin AR, Orogo-Wenn MC, Walters DV Abstract Tight control of lung liquid regulation is vital for pulmonary function. The aim of this work was to determine whether PKC activation is involved in the physiological regulation of lung liquid volume in a whole lung preparation. Rat lungs were perfused with a modified Ringer's solution and the lumen filled with the same solution, with the exclusion of glucose. Lung liquid (LL) volume was measured during a control period and after modulating drugs were administered and net LL trans-epithelial movement (J(v)) was calculated. When the PKC activator, phorbol 12-myristate 13-acetate (PMA 10(-5) M) and the calcium ionophore, ionomycin (10(-6) M) were instilled into the lung together, J(v) was significantly reduced (p=0.03... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5281397 Fri, 23 Sep 2011 04:00:00 +0100 5281397 http://www.medworm.com/index.php?rid=5247303&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21926263%26dopt%3DAbstract Authors: Olson N, Hristova M, Heintz NH, Lounsbury KM, Van Der Vliet A Abstract The respiratory epithelium forms an important barrier against inhaled pollutants and microorganisms and its barrier function is often compromised during inflammatory airway diseases. Epithelial activation of hypoxia inducible factor 1 (HIF-1) represents one feature of airway inflammation, but the functional importance of HIF-1 within the respiratory epithelium is largely unknown. Using primary mouse tracheal epithelial (MTE) cells or immortalized human bronchial epithelial cells (16HBE14o-), we evaluated the impact of HIF-1 activation on loss of epithelial barrier function during oxidative stress. Exposure of either 16HBE14o- or MTE cells to H(2)O(2) resulted in significant loss of transepithelial elect... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5247303 Fri, 16 Sep 2011 04:00:00 +0100 5247303 http://www.medworm.com/index.php?rid=5247302&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21926264%26dopt%3DAbstract This study tested the hypothesis that there is functional interaction between TGF-β/Smad signaling pathway and PPARγ in isolated pulmonary artery small muscle cells (PASMCs) under hypoxic stress. We observed that chronic hypoxic led to a dramatic decrease of PPARγ protein expression in whole lung homogenates (rat and mouse) and hypertrophied pulmonary arteries and isolated PASMCs. Using a transgenic model of mouse with inducible overexpression of a dominant negative mutant of TGF-β receptor type II, we demonstrated that disruption of TGF-β pathway significantly attenuated chronic hypoxia-induced downregulation of PPARγ in lung. Similarly, in isolated rat PASMCs, antagonism of TGF-β signaling with either a neutralizing antibody to TGF-β or the selective TGF-β receptor type I inhibi... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5247302 Fri, 16 Sep 2011 04:00:00 +0100 5247302 http://www.medworm.com/index.php?rid=5247301&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21926265%26dopt%3DAbstract Authors: Kang BY, Kleinhenz JM, Murphy TC, Hart CM Abstract PPARγ activation attenuated hypoxia-induced pulmonary hypertension (PH) in mice although the mechanisms for these effects remain to be completely defined. We hypothesized that PPARγ attenuates hypoxia-induced endothelin-1 (ET-1) signaling. Human pulmonary artery endothelial cells (HPAECs) were exposed to hypoxia (1% O(2)) or normoxia for 72 h and treated ± the PPARγ ligand, rosiglitazone (RSG, 10 μM), during the last 24 h. Selected HPAECs were treated with chetomin (HIF-1α inhibitor, 25 nM) or with caffeic acid phenethyl ester (CAPE, NF-kB inhibitor, 20 μM) for 3 h. HPAEC proliferation was measured with MTT assays or cell counting. Male C57BL/6 mice were exposed to hypoxia (10% O(2)) or normoxia (21% O(2)) for 3 wk ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5247301 Fri, 16 Sep 2011 04:00:00 +0100 5247301 http://www.medworm.com/index.php?rid=5247300&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21926266%26dopt%3DAbstract Conclusion: Contractile PA myocytes exhibit marked Rho-dependent APM in hypoxia, with increased active RhoA and LIMK phosphorylation. Their additional APM response to U46619 challenge is independent of RhoA, reflecting decreased TP association with Gα12/13 in favor of Gαq. In contrast, hypoxic contractile Ao myocytes polymerize actin modestly, and depolymerize to U46619. Both basal APM, and the APM response to U46619, are increased in PPHN PA. APM corresponds with increased force generation to U46619 challenge in PPHN PA, but not renal arteries. PMID: 21926266 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5247300 Fri, 16 Sep 2011 04:00:00 +0100 5247300 http://www.medworm.com/index.php?rid=5247299&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21926267%26dopt%3DAbstract Authors: Miyamoto S, Hattori N, Senoo T, Onari Y, Iwamoto H, Kanehara M, Ishikawa N, Fujitaka K, Haruta Y, Murai H, Yokoyama A, Kohno N Abstract Recent studies suggest that plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of the fibrinolytic system, may promote the development of asthma. To further investigate the significance of PAI-1 in the pathogenesis of asthma and determine the possibility that PAI-1 could be a therapeutic target for asthma, this study was conducted. First, PAI-1 levels in induced sputum (IS) from asthmatics and healthy controls were measured. In asthmatics, IS PAI-1 levels were elevated compared with healthy controls, and were significantly higher in patients with long duration asthma compared to short duration asthma. PAI-1 levels were also found... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5247299 Fri, 16 Sep 2011 04:00:00 +0100 5247299 http://www.medworm.com/index.php?rid=5219240&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21908587%26dopt%3DAbstract Authors: Maille E, Trinh NT, Prive A, Bilodeau C, Bissonnette E, Grandvaux N, Brochiero E Abstract Chronic infection and inflammation have been associated with progressive airway epithelial damage in cystic fibrosis (CF) patients. However, the effect of inflammatory products on the repair capacity of respiratory epithelia is unclear. Our objective was to study the regulation of repair mechanisms by tumor necrosis factor-alpha (TNFα), a major component of inflammation in CF, in a model of mechanical wounding, in 2 bronchial cell lines, non-CF NuLi and CF CuFi. We observed that TNFα enhanced the NuLi and CuFi repair rates. Chronic exposure (24-48 h) to TNFα augmented this stimulation as well as the migration rate during repair. The cellular mechanisms involved in this stimulation ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5219240 Fri, 09 Sep 2011 04:00:00 +0100 5219240 http://www.medworm.com/index.php?rid=5219239&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21908588%26dopt%3DAbstract In this study, we investigated the activation of β-catenin signaling and its contribution to ECM production by airway smooth muscle cells in response to TGF-β(1). Stimulation of airway smooth muscle cells with TGF-β(1) resulted in a time-dependent increase of total and non-phosphorylated β-catenin protein expression via induction of β-catenin mRNA and inhibition of GSK-3. In addition, the TGF-β(1)-induced β-catenin activated TCF/LEF-dependent gene transcription, as determined by the β-catenin sensitive TOP-flash luciferase reporter assay. Furthermore, TGF-β(1) stimulation increased mRNA expression of collagen Iα1, fibronectin, versican and PAI-1. Pharmacological inhibition of β-catenin by PKF115-584 or down regulation of β-catenin expression by specific siRNA substantially inhi... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5219239 Fri, 09 Sep 2011 04:00:00 +0100 5219239 http://www.medworm.com/index.php?rid=5219238&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21908589%26dopt%3DAbstract Authors: Delaney C, Gien J, Grover TR, Roe GB, Abman SH Abstract Maternal use of selective serotonin reuptake inhibitors (SSRIs) is associated with an increased risk for persistent pulmonary hypertension of the newborn (PPHN) but little is known about serotonin (5-HT) signaling in the developing lung. We hypothesize that 5-HT plays a key role in maintaining high pulmonary vascular resistance (PVR) in the fetus, and that fetal exposure to SSRIs increases 5-HT activity and causes pulmonary hypertension. We studied the hemodynamic effects of 5-HT, 5-HT receptor antagonists, and SSRIs in chronically prepared fetal sheep. Brief infusions of 5-HT (3-20 μg) increased PVR in a dose-related fashion. Ketanserin, a 5-HT 2A receptor antagonist, caused pulmonary vasodilation and inhibited 5-HT... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5219238 Fri, 09 Sep 2011 04:00:00 +0100 5219238 http://www.medworm.com/index.php?rid=5219237&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21908590%26dopt%3DAbstract This study has shown that, when cultured type II pneumocytes are exposed to lipoprotein-free serum (LFS), the level of lyso-phosphatidylcholine (lyso-PC) in the secreted surfactant phospholipids is markedly elevated with a concomitant decline in the level of phosphatidylcholine (PC). This effect is the result of hydrolysis of surfactant phosphatidylcholine by a phospholipase A(2) (PLA(2))-like activity present within serum. Anion-exchange chromatography, gel filtration chromatography and preparative electrophoresis of human LFS have shown that this PLA(2)-like activity co-elutes with albumin and is biochemically distinct from the secretory form of PLA(2). Furthermore, specific inhibitors of PLA(2) such as p bromophenacyl bromide, aristolochic acid, palmitoyl trifluoromethyl ketone do not i... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5219237 Fri, 09 Sep 2011 04:00:00 +0100 5219237 http://www.medworm.com/index.php?rid=5219236&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21908591%26dopt%3DAbstract Authors: Weng M, Baron DM, Bloch KD, Luster AD, Lee JJ, Medoff BD Abstract There is increasing evidence that inflammation plays a pivotal role in the pathogenesis of some forms of pulmonary hypertension (PH). We recently demonstrated that deficiency of adiponectin (APN) in a mouse model of PH induced by eosinophilic inflammation increases pulmonary arterial remodeling, pulmonary pressures, and the accumulation of eosinophils in the lung. Based on these data, we hypothesized that APN-deficiency exacerbates PH indirectly by increasing eosinophil recruitment. Herein, we examined the role of eosinophils in the development of inflammation-induced PH. Elimination of eosinophils in APN-deficient mice by treatment with anti-interleukin-5 antibody attenuated pulmonary arterial muscularizati... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5219236 Fri, 09 Sep 2011 04:00:00 +0100 5219236 http://www.medworm.com/index.php?rid=5219235&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21908592%26dopt%3DAbstract Authors: Bierer R, Nitta CH, Friedman JK, Codianni SJ, de Frutos S, Dominguez-Bautista JA, Howard TA, Resta TC, Gonzalez Bosc LV Abstract Pulmonary hypertension occurs with prolonged exposure to chronic hypoxia in both adults and neonates. The Ca(2+)-dependent transcription factor nuclear factor of activated T-cells isoform c3 (NFATc3) has been implicated in chronic hypoxia-induced pulmonary arterial remodeling in adult mice. Therefore, we hypothesized that NFATc3 is required for chronic hypoxia-induced pulmonary hypertension in adult and neonatal mice. The aim of this study was to determine if: 1) NFATc3 mediates chronic hypoxia-induced increases in right ventricular systolic pressure in adult mice, 2) NFATc3 is activated in neonatal mice exposed to chronic hypoxia, and 3) NFATc3 ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5219235 Fri, 09 Sep 2011 04:00:00 +0100 5219235 http://www.medworm.com/index.php?rid=5219243&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21890510%26dopt%3DAbstract CHRONIC HYPOXIA-INDUCED ACID-SENSITIVE ION CHANNEL EXPRESSION IN CHEMOAFFERENT NEURONS CONTRIBUTES TO CHEMORECEPTOR HYPERSENSITIVITY. Am J Physiol Lung Cell Mol Physiol. 2011 Sep 2; Authors: Liu X, He L, Dinger B, Fidone SJ Abstract Previously we demonstrated that chronic hypoxia (CH) induces an inflammatory condition characterized by immune cell invasion and increased expression of inflammatory cytokines in rat carotid body. It is well established that chronic inflammatory pain induces the expression of acid-sensitive ion channels (ASIC) in primary sensory neurons, where they contribute to hyperalgesia and allodynia. The current study examines the effect of CH on ASIC expression in petrosal ganglion (PG), which contains chemoafferent neurons that innervate oxygen-sensitive... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5219243 Fri, 02 Sep 2011 04:00:00 +0100 5219243 http://www.medworm.com/index.php?rid=5219242&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21890511%26dopt%3DAbstract Authors: Brew N, Hooper SB, Allison BJ, Wallace MJ, Harding R Abstract Mechanical ventilation (MV) of very premature infants contributes to lung injury and bronchopulmonary dysplasia (BPD), the effects of which can be long-lasting. Little is currently known about the ability of the very immature lung to recover from ventilator- induced lung injury. Our objective was to determine the ability of the injured very immature lung to repair in the absence of continued ventilation and to identify potential mechanisms. At 125 days gestational age (d GA, 0.85 of term) fetal sheep were partially exposed by hysterectomy under anesthesia and aseptic conditions; they were intubated and ventilated for 2 hours with an injurious MV protocol, and then returned to the uterus to continue development. ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5219242 Fri, 02 Sep 2011 04:00:00 +0100 5219242 http://www.medworm.com/index.php?rid=5219241&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21890512%26dopt%3DAbstract MITOCHONDRIAL DNA INTEGRITY MAY BE A DETERMINANT OF ENDOTHELIAL BARRIER PROPERTIES IN OXIDANT-CHALLENGED RAT LUNGS. Am J Physiol Lung Cell Mol Physiol. 2011 Sep 2; Authors: Chouteau JM, Obiako B, Gorodnya OM, Pastukh VM, Ruchko MV, Wright AJ, Wilson GL, Gillespie MN Abstract In cultured pulmonary artery endothelial cells and other cell types, over-expression of mt-targeted DNA repair enzymes protects against oxidant-induced mitochondrial DNA (mtDNA) damage and cell death. Whether mtDNA integrity governs functional properties of the endothelium in the intact pulmonary circulation is unknown. Accordingly, the present study used isolated, buffer-perfused rat lungs to determine if fusion proteins targeting 8-oxoguanine DNA glycosylase 1 (Ogg1) or endonuclease III (Endo III) to ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5219241 Fri, 02 Sep 2011 04:00:00 +0100 5219241 http://www.medworm.com/index.php?rid=5176730&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21873444%26dopt%3DAbstract In conclusion, soluble components of CS have direct endothelial barrier disruptive effects which could be ameliorated by glutathione modulators or by inhibitors of neutral sphingomyelinase, p38 MAPK, JNK, and Rho kinase. Amelioration of endothelial permeability may alleviate lung and systemic vascular dysfunction associated with smoking-related chronic obstructive lung diseases. PMID: 21873444 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5176730 Thu, 25 Aug 2011 23:00:00 +0100 5176730 http://www.medworm.com/index.php?rid=5176729&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21873445%26dopt%3DAbstract Authors: Roan E, Waters CM Abstract The pulmonary alveolus, terminal gas-exchange unit of the lung, is composed of alveolar epithelial (AE) and endothelial cells separated by a thin basement membrane and interstitial space. These cells participate in the maintenance of a delicate system regulated not only by biological factors, but also by the mechanical environment of the lung, which undergoes dynamic deformation during breathing. Clinical and animal studies as well as cell culture studies point toward a strong influence of mechanical forces on lung cells and tissues including effects on growth and repair, surfactant release, injury, and inflammation. However, despite substantial advances in our understanding of lung mechanics over the last half century, there are still many unans... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5176729 Thu, 25 Aug 2011 23:00:00 +0100 5176729 http://www.medworm.com/index.php?rid=5176728&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21873446%26dopt%3DAbstract INTRAUTERINE GROWTH RESTRICTION DECREASES PULMONARY ALVEOLAR AND VESSEL GROWTH AND CAUSES PULMONARY ARTERY ENDOTHELIAL CELL DYSFUNCTION IN VITRO IN FETAL SHEEP. Am J Physiol Lung Cell Mol Physiol. 2011 Aug 26; Authors: Rozance PJ, Seedorf GJ, Brown A, Roe GB, O'Meara MC, Gien J, Tang JR, Abman SH Abstract Intrauterine growth restriction (IUGR) increases the risk for bronchopulmonary dysplasia (BPD). Abnormal lung structure has been noted in animal models of IUGR but whether IUGR adversely impacts fetal pulmonary vascular development and pulmonary artery endothelial cell (PAEC) function is unknown. We hypothesized that IUGR would decrease fetal pulmonary alveolarization, vascular growth and in vitro PAEC function. Studies were performed in an established model of severe plac... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5176728 Thu, 25 Aug 2011 23:00:00 +0100 5176728 http://www.medworm.com/index.php?rid=5176727&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21873447%26dopt%3DAbstract Authors: Pera T, Sami R, Zaagsma J, Meurs H Abstract Increased airway smooth muscle (ASM) mass is a major feature of airway remodeling in asthma and COPD. Growth factors induce an ASM phenotype, characterized by an increased proliferative state and a decreased contractile protein expression, reducing contractility of the muscle. TGF-β-activated kinase 1 (TAK1), a mitogen-activated protein kinase kinase kinase (MAP3K7), is a key enzyme in pro-inflammatory signaling in various cell types; however, its function in ASM is unknown. The aim of this study was to investigate the role of TAK1 in growth factor-induced phenotypic modulation of ASM. Using bovine tracheal smooth muscle (BTSM) strips and -cells, as well as human tracheal smooth muscle cells (HTSM) cells, we investigated the rol... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5176727 Thu, 25 Aug 2011 23:00:00 +0100 5176727 http://www.medworm.com/index.php?rid=5176726&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21873448%26dopt%3DAbstract Authors: Kooijman EE, Kuzenko SR, Gong D, Best MD, Folkesson HG Abstract Cell membrane phospholipids, like phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)), can regulate epithelial Na channel (ENaC) activity. Gender differences in lung ENaC expression have also been demonstrated. However, the effects in vivo on alveolar fluid clearance are uncertain. Thus, PI(4,5)P(2) effects on alveolar fluid clearance were studied in male and female rats. An isosmolar 5% albumin solution was intrapulmonary instilled; alveolar fluid clearance was studied for 1 h. Female rats had a 37 ± 19% higher baseline alveolar fluid clearance than male rats. Bilateral ovariectomy attenuated this gender difference. Compared to controls, PI(4,5)P(2)-instillation (300 µM) increased alveolar fluid clearance b... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5176726 Thu, 25 Aug 2011 23:00:00 +0100 5176726 http://www.medworm.com/index.php?rid=5176725&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21873449%26dopt%3DAbstract Authors: O'Dea KP, Dokpesi JO, Tatham KC, Wilson MR, Takata M Abstract Margination and activation of monocytes within the pulmonary microcirculation contributes substantially to the development of acute lung injury in mice. The enhanced LPS-induced TNF expression exhibited by Gr-1(high) compared to Gr-1(low) monocytes within the lung microvasculature suggests differential roles for these subsets. We investigated the mechanisms responsible for such heterogeneity of lung-marginated monocyte pro-inflammatory response using a combined in vitro and in vivo approach. The monocyte subset inflammatory response was studied in vitro in mouse PBMC-lung endothelial cell coculture, and in vivo in a two-hit model of i.v. LPS-induced monocyte margination and lung inflammation in mice, by flow cyt... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5176725 Thu, 25 Aug 2011 23:00:00 +0100 5176725 http://www.medworm.com/index.php?rid=5176724&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21873450%26dopt%3DAbstract Authors: Luciw PA, Oslund KL, Yang XW, Adamson L, Ravindran R, Canfield DR, Tarara R, Hirst L, Christensen M, Lerche NW, Offenstein H, Lewinsohn D, Ventimiglia F, Brignolo L, Wisner ER, Hyde DM Abstract Infection with Mycobacterium tuberculosis primarily produces a multifocal distribution of pulmonary granulomas in which the pathogen resides. Accordingly, quantitative assessment of the bacterial load and pathology is a substantial challenge in tuberculosis. Such assessments are critical for studies of the pathogenesis and for the development of vaccines and drugs in animal models of experimental M. tuberculosis infection. Stereology enables unbiased quantitation of 3-dimensional objects from 2-dimensional sections and thus is suited to quantify histologic lesions. We have developed... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5176724 Thu, 25 Aug 2011 23:00:00 +0100 5176724 http://www.medworm.com/index.php?rid=5176723&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21873451%26dopt%3DAbstract AIRWAY REMODELING IN MURINE ASTHMA CORRELATES WITH A DEFECT IN PGE2 SYNTHESIS BY LUNG FIBROBLASTS. Am J Physiol Lung Cell Mol Physiol. 2011 Aug 26; Authors: Stumm CL, Wettlaufer SH, Jancar S, Peters-Golden M Abstract Asthma is a chronic lung disease characterized by local inflammation which can result in structural alterations termed airway remodeling. One component of airway remodeling involves fibroblast accumulation and activation, resulting in deposition of collagen I around small bronchi. Prostaglandin E(2) (PGE(2)) is the main eicosanoid lipid mediator produced by lung fibroblasts and it exerts diverse anti-fibrotic actions. Dysregulation of the PGE(2) synthesis/response axis has been identified in human pulmonary fibrotic diseases and implicated in the pathogenesis o... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5176723 Thu, 25 Aug 2011 23:00:00 +0100 5176723 http://www.medworm.com/index.php?rid=5157516&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21856812%26dopt%3DAbstract Authors: Pitt BR, Christman JW, Gunst SJ, Matthay MA, Stevens T, Ware LB Abstract NONE. PMID: 21856812 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5157516 Thu, 18 Aug 2011 23:00:00 +0100 5157516 http://www.medworm.com/index.php?rid=5157515&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21856813%26dopt%3DAbstract Authors: Zhang G, Nie H, Yang J, Ding X, Huang Y, Yu H, Li R, Yuan Z, Hu S Abstract Asthma is a common chronic inflammatory disease involving many different cell types. Recently, type I natural killer T (NKT) cells have been demonstrated to play a crucial role in the development of asthma. However, the roles of type II NKT cells in asthma have not been investigated before. Interestingly, type I and type II NKT cells have been shown to have opposing roles in anti-tumor immunity, anti-parasite immunity, and autoimmunity. We hypothesized that sulfatide-activated type II NKT cells could prevent allergic airway inflammation by inhibiting type I NKT cell function in asthma. Strikingly, in our mouse model, activation of type II NKT cells by sulfatide administration and adoptive transfer o... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5157515 Thu, 18 Aug 2011 23:00:00 +0100 5157515 http://www.medworm.com/index.php?rid=5157514&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21856814%26dopt%3DAbstract In this study, we examined the signaling mechanism for SRF activation by TGF-beta as it relates to pulmonary myofibroblast differentiation. TGF-beta stimulated a profound, but delayed (18-24 hours), activation of Rho kinase and formation of actin stress fibers, which paralleled SM alpha-actin expression. The translational inhibitor cycloheximide blocked these processes without affecting Smad-dependent gene transcription. Inhibition of Rho kinase by Y27632 or depolymerization of actin by latrunculin-B resulted in inhibition TGF-beta-induced SRF activation and SM alpha-actin expression, having no effect on Smad signaling. Conversely, stabilization of actin stress fibers by jasplakinolide was sufficient to drive these processes in the absence of TGF-beta. TGF-beta promoted a delayed nuclear a... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5157514 Thu, 18 Aug 2011 23:00:00 +0100 5157514 http://www.medworm.com/index.php?rid=5157513&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21856815%26dopt%3DAbstract Conclusions: The use of PEEP during initiation of ventilation at birth decreased early mediators of lung injury. Surfactant administration changed the distribution of injury and had a moderate additive protective effect. PMID: 21856815 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5157513 Thu, 18 Aug 2011 23:00:00 +0100 5157513 http://www.medworm.com/index.php?rid=5157512&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21856816%26dopt%3DAbstract Authors: Yasuda T, Tada Y, Tanabe N, Tatsumi K, West J Abstract Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by a sustained elevation in the pulmonary artery pressure and subsequent right heart failure. The activation of Rho/Rho-kinase activity and the beneficial effect of Rho-kinase inhibition have been demonstrated in several experimental models of pulmonary hypertension. However, it remains unclear whether Rho-kinase inhibitors can also be used against pulmonary hypertension associated with mutations in the type II bone morphogenetic protein receptor (BMPRII) gene. Transgenic mice expressing a dominant-negative BMPRII gene (with an arginine to termination mutation at amino acid 899) in smooth muscle by a tetracycline-gene switch system (SM22-... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5157512 Thu, 18 Aug 2011 23:00:00 +0100 5157512 http://www.medworm.com/index.php?rid=5157511&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21856817%26dopt%3DAbstract Authors: Chester MA, Seedorf GJ, Tourneux P, Gien J, Tseng N, Grover TR, Wright J, Stasch JP, Abman SH Abstract Although inhaled NO therapy is often effective in treating infants with PPHN, up to 40% of patients fail to respond, which may be partly due to abnormal expression and function of soluble guanylate cyclase (sGC). To determine whether altered sGC expression or activity due to oxidized sGC contributes to high PVR and poor NO responsiveness, we studied the effects of cinaciguat (BAY 58-2667), an sGC activator, on pulmonary artery smooth muscle cells (PASMC) from normal fetal sheep and sheep exposed to chronic intrauterine pulmonary hypertension (PPHN). We found increased sGC α1 and β1 subunit protein expression but lower basal cGMP levels in PPHN PASMC when compared to nor... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5157511 Thu, 18 Aug 2011 23:00:00 +0100 5157511 http://www.medworm.com/index.php?rid=5157510&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21856818%26dopt%3DAbstract Authors: Day RM, Lee YH, Han L, Kim YC, Feng YH Abstract At the cellular level, 5'-AMP-activated protein kinase (AMPK) serves as a critical link between energy homeostasis and the regulation of fundamental biological activities, including apoptosis. Angiotensin (Ang) II plays a key role in fibrotic lung remodeling. We recently demonstrated that Ang II induces apoptosis in pulmonary artery endothelial cells (PAEC) through the angiotensin type 2 receptor (AT(2)). AT(2) activates Src-homology 2 domain containing phosphatase-2 (SHP-2) in a signaling cascade leading to Bcl-x(L) mRNA destabilization and initiation of intrinsic apoptosis. We investigated the requirement of AMPK and ATP generation for Ang II-induced apoptosis in PAEC. Ang II activated AMPK, which was required for ATP gener... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5157510 Thu, 18 Aug 2011 23:00:00 +0100 5157510 http://www.medworm.com/index.php?rid=5157509&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21856819%26dopt%3DAbstract In this study, an established model of pulmonary fibrosis was used in which 10-12 week old male C57BL/6 mice were administered a single dose (1.0 mg/kg) of bleomycin via oropharyngeal aspiration. To test the role of prostaglandins in this model, mice were dosed, via surgically-implanted minipumps, with either vehicle, PGE(2) (1.32 μg/hour) or the prostacyclin analog iloprost (0.33 μg/hour) beginning 7 days before or 14 days after bleomycin administration. Endpoints assessed at 7 days after bleomycin administration included pro-inflammatory cytokine levels and measurement of cellular infiltration into the lung. Endpoints assessed at 21 days after bleomycin administration included lung function assessment via invasive (FlexiVent) analysis, cellular infiltration, lung collagen content, and ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5157509 Thu, 18 Aug 2011 23:00:00 +0100 5157509 http://www.medworm.com/index.php?rid=5141611&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840960%26dopt%3DAbstract Authors: Rowe RG, Keena D, Sabeh F, Willis AL, Weiss SJ Abstract In acute and chronic lung disease, widespread disruption of tissue architecture underlies compromised pulmonary function. Pulmonary fibroblasts have been implicated as critical effectors of tissue-destructive extracellular matrix (ECM) remodeling by mobilizing a spectrum of proteolytic enzymes. While efforts to date have focused on the catabolism of type I collagen - the predominant component of the lung interstitial matrix - the key collagenolytic enzymes employed by pulmonary fibroblasts remain unidentified. Herein, membrane type-1 matrix metalloprotease (MT1-MMP) is identified as the dominant, and direct-acting, protease responsible for the type I collagenolytic activity mediated by both mouse and human pulmonary f... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5141611 Thu, 11 Aug 2011 23:00:00 +0100 5141611 http://www.medworm.com/index.php?rid=5141610&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840961%26dopt%3DAbstract This study will add to our understanding of the pathophysiological roles of extracellular nucleotides in the lung. PMID: 21840961 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5141610 Thu, 11 Aug 2011 23:00:00 +0100 5141610 http://www.medworm.com/index.php?rid=5141609&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840962%26dopt%3DAbstract Authors: Silveyra P, Raval M, Simmons BP, Diangelo S, Wang G, Floros J Abstract Two human genes, SFTPA1 (SP-A1), SFTPA2 (SP-A2), encode surfactant protein A, a molecule of innate immunity and surfactant-related functions. Several genetic variants have been identified for both genes. These include nucleotide (nt) polymorphisms, as well as alternative splicing patterns at the 5'UTR. Exon B (eB) is included in the 5'UTR of most SP-A2, but not SP-A1 splice variants. We investigated the role of eB in the regulation of gene expression, and translation efficiency. A luciferase (Luc) reporter gene was cloned downstream of the entire (AeBD) or eB deletion mutants (del_mut) of the SP-A2 5'UTR, or heterologous 5'UTRs containing the eB sequence, or a random sequence of equal length. The del_mu... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5141609 Thu, 11 Aug 2011 23:00:00 +0100 5141609 http://www.medworm.com/index.php?rid=5141608&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840963%26dopt%3DAbstract Authors: Lei J, Ingbar DH Abstract We previously reported that the T3-induced increase of Na,K-ATPase activity in rat alveolar epithelial cells (AECs) required activation of Src kinase, PI3K and MAPK/ERK1/2. In the current study, we assessed the role of Akt in Na,K-ATPase activity and the interaction between the PI3K and MAPK in response to T3 with using MP48 cells, inhibitors and constitutively active mutants in the MP48 (alveolar type II-like) cell line. The Akt inhibitor VIII blocked T3-induced increases in Na,K-ATPase activity and amount of plasma membrane Na,K-ATPase protein. The Akt inhibitor VIII also abolished the increase in Na,K-ATPase activity induced by constitutively active mutants of either Src kinase or PI3K. Moreover, constitutively active mutants of Akt increased N... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5141608 Thu, 11 Aug 2011 23:00:00 +0100 5141608 http://www.medworm.com/index.php?rid=5141616&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21821727%26dopt%3DAbstract Authors: Eldridge L, Moldobaeva A, Wagner EM Abstract Hyaluronan (HA), a glycosaminoglycan critical to the lung extracellular matrix, has been shown to dissociate into low molecular weight (LMW) HA fragments following exposure to injurious stimuli. In the present study we questioned whether lung HA changed during ischemia and if changes had an effect on subsequent angiogenesis. After left pulmonary artery ligation (LPAL) in mice, we analyzed left lung homogenates immediately after the onset of ischemia (0 h) and intermittently for 14 days. The relative expression of hyaluronan synthase (HAS)1, HAS2 and HAS3 were determined using real-time RT PCR, total HA in the lung was measured by an ELISA-like assay, gel electrophoresis was performed to determine changes in HA size distribution,... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5141616 Thu, 04 Aug 2011 23:00:00 +0100 5141616 http://www.medworm.com/index.php?rid=5141615&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21821728%26dopt%3DAbstract Authors: Zhao J, He D, Su Y, Berdyshev EV, Chun J, Natarajan V, Zhao Y Abstract Lysophosphatidic acid (LPA), a bioactive phospholipid, plays an important role in lung inflammation by inducing the release of chemokines and lipid mediators. Our previous studies have shown that LPA induces the secretion of interleukin-8 and PGE2 in lung epithelial cells. Here, we demonstrate that LPA receptors contribute to lipopolysaccharide (LPS)-induced inflammation. Pretreatment with LPA receptor antagonist, ki16425 or downregulation of LPA receptor 1 (LPA(1)) by siRNA attenuated LPS-induced phosphorylation of p38 MAPK, I-ĸB kinase, and I-ĸB in MLE12 epithelial cells. In addition, the blocking of LPA(1) also suppressed LPS-induced IL-6 production. Furthermore, LPS treatment promoted interaction ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5141615 Thu, 04 Aug 2011 23:00:00 +0100 5141615 http://www.medworm.com/index.php?rid=5141614&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21821729%26dopt%3DAbstract Authors: Sakurai R, Li Y, Torday JS, Rehan VK Abstract There is no effective intervention to prevent or treat Bronchopulmonary Dysplasia (BPD). Curcumin has potent antioxidant and anti-inflammatory properties, and it modulates peroxisome proliferator-activated receptor gamma (PPARγ) signaling, an important molecule in the pathobiology of BPD. However, its role in the prevention of BPD is not known. We determined if curcumin i) enhances neonatal lung maturation; ii) protects against hyperoxia-induced neonatal lung injury; and iii) if this protection is mediated by blocking TGF-β. Embryonic day 19 (e19) fetal rat lung fibroblasts were exposed to either 21% or 95% O(2) for 24h following 1h pretreatment with curcumin. Curcumin dose-dependently accelerated e19 fibroblast differentiati... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5141614 Thu, 04 Aug 2011 23:00:00 +0100 5141614 http://www.medworm.com/index.php?rid=5141613&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21821730%26dopt%3DAbstract Authors: Senouvo FY, Tabet Y, Morin CS, Albadine R, Sirois C, Rousseau E Abstract Epoxyeicosatrienoic acid and thromboxane A(2) are arachidonic-acid derivatives. The former has initially been defined as an epithelium-derived hyperpolarizing factor (EDHF) displaying broncho-relaxing (4) and anti-inflammatory properties, as recently demonstrated (25), whereas thromboxane A(2) induces vaso- and bronchoconstriction upon binding to TP-receptor. Epoxyeicosatrienoic acids, however, are quickly degraded by the soluble epoxide hydrolase (sEH) into inactive diol compounds (25). The aim of this study was to investigate the effects of 14, 15-epoxy-eicosatrienoic acid (EET) on thromboxane-prostanoid receptor (TP-receptor) activation in human bronchi. Tension measurements performed on native bro... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5141613 Thu, 04 Aug 2011 23:00:00 +0100 5141613 http://www.medworm.com/index.php?rid=5141612&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21821731%26dopt%3DAbstract Authors: Del Rio R, Muñoz C, Arias P, Court FA, Moya EA, Iturriaga R Abstract Chronic intermittent hypoxia (CIH), a characteristic of sleep obstructive apnea, enhances carotid body (CB) chemosensory responses to hypoxia, but its consequences on CB vascular area and VEGF expression are unknown. Accordingly, we studied the effect of CIH on CB volume, glomus cell numbers, blood vessels diameter and number, and VEGF immunoreactivity (VEGF-ir) in male Sprague-Dawley rats exposed to 5%O(2), 12 times/hr for 8 hrs or sham condition for 21 days. We found that CIH did not modify the CB volume or the number of glomus cells, but increased VEGF-ir and enlarged the vascular area by increasing the size of the blood vessels, while the number of the vessels was unchanged. Since oxidative stress pl... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5141612 Thu, 04 Aug 2011 23:00:00 +0100 5141612 http://www.medworm.com/index.php?rid=5103964&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803868%26dopt%3DAbstract This study identifies an alternative pathway to paracrine signaling to convey regulatory signals from PAECs to PASMCs, and raises the possibility that dysregulation of this direct interaction is involved in the pathogenesis of hypertensive pulmonary vascular remodeling. PMID: 21803868 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5103964 Thu, 28 Jul 2011 23:00:00 +0100 5103964 http://www.medworm.com/index.php?rid=5103963&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803869%26dopt%3DAbstract We examined these associations by subjecting murine neonatal lung tissue with and without IUS to quantitative PCR (N = 4 - 14 per group). Our murine model showed that IUS decreased RUNX expression at P3 and P5 (P < 0.05). We conclude that 1) SNPs in RUNX1 are associated with airway responsiveness in asthmatic children and these associations are modified by IUS exposure, 2) IUS tended to increase the expression of RUNX1 in early human development, and 3) a murine IUS model showed that the effects of developmental cigarette smoke exposure persisted for at least 2 weeks after birth. We speculate that IUS exposure altered expression of RUNX transcription factors increases the risk of asthma in children with IUS exposure. PMID: 21803869 [PubMed - as supplied by publisher] (Source: Americ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5103963 Thu, 28 Jul 2011 23:00:00 +0100 5103963 http://www.medworm.com/index.php?rid=5103962&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803870%26dopt%3DAbstract CAVEOLIN-1 IN CYTOKINE-INDUCED ENHANCEMENT OF INTRACELLULAR CA2+ IN HUMAN AIRWAY SMOOTH MUSCLE. Am J Physiol Lung Cell Mol Physiol. 2011 Jul 29; Authors: Sathish V, Abcejo AJ, Vanoosten SK, Thompson MA, Prakash YS, Pabelick CM Diseases such as asthma are characterized by airway hyperresponsiveness. Enhanced airway smooth muscle (ASM) intracellular Ca(2+) ([Ca(2+)](i)) response to agonist stimulation leading to increased airway constriction has been suggested to contribute to airway hyperresponsiveness. Caveolae are flask-shaped plasma membrane invaginations that express the scaffolding protein caveolin and contain multiple proteins important in [Ca(2+)](i) signaling (e.g. agonist receptors, ion channels). We recently demonstrated that caveolae and caveolin-1 are important in [C... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5103962 Thu, 28 Jul 2011 23:00:00 +0100 5103962 http://www.medworm.com/index.php?rid=5103961&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803871%26dopt%3DAbstract The objective of the current study was to test the hypothesis that IH augments ET-1 induced pulmonary vasoconstrictor reactivity through a PKCβ-dependent signaling pathway. Responses to ET-1 were assessed in endothelium-disrupted, pressurized pulmonary arteries (~150 μm inner diameter) from eucapnic-IH [(E-IH) 3 min cycles, 5% O(2), 5% CO(2)/air flush, 7 hr/day; 4 wk] and sham (air cycled) rats. Arteries were loaded with fura-2 AM to monitor vascular smooth muscle (VSM) intracellular Ca(2+) concentration ([Ca(2+)](i)). E-IH increased vasoconstrictor reactivity without altering Ca(2+) responses, suggestive of myofilament Ca(2+) sensitization. Consistent with our hypothesis, inhibitors of both PKCα/β (myr-PKC) and PKCβ (LY-333-531) selectively decreased vasoconstriction to ET-1 in arter... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5103961 Thu, 28 Jul 2011 23:00:00 +0100 5103961 http://www.medworm.com/index.php?rid=5103969&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21784966%26dopt%3DAbstract Conclusions: In the OVA-sensitized and -challenged mouse model of allergic asthma, aerosolized GSNO has rapid and sustained anti-bronchoconstrictive effects but does not substantially alter airway inflammation. Supported by NIH LG Que (HL086887). PMID: 21784966 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5103969 Thu, 21 Jul 2011 23:00:00 +0100 5103969 http://www.medworm.com/index.php?rid=5103968&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21784967%26dopt%3DAbstract Authors: England KA, Price AP, Tram KV, Shapiro SD, Blazar BR, Panoskaltsis-Mortari A Idiopathic Pneumonia Syndrome (IPS) is a significant cause of morbidity and mortality post-BMT in humans. In our established murine IPS model in which lethally conditioned recipients are given allogeneic bone marrow and splenocytes, recruitment of host monocytes occurs early post-BMT, followed by donor T cells concomitant with development of severe lung dysfunction. Since MMP12 is important for macrophage infiltration and injury in other mouse models of lung disease such as emphysema, lethally conditioned MMP12(-/-) mice were used as allogeneic recipients to determine if MMP12 plays a similar role in potentiating lung injury in IPS. Surprisingly, MMP12(-/-) mice developed IPS and exhibited an accelera... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5103968 Thu, 21 Jul 2011 23:00:00 +0100 5103968 http://www.medworm.com/index.php?rid=5103967&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21784968%26dopt%3DAbstract Authors: Wang Y, Voelker DR, Lugogo NL, Wang G, Floros J, Ingram JL, Chu HW, Church TD, Kandasamy P, Fertel D, Wright JR, Kraft M ABSTRACT Surfactant protein A (SP-A) regulates a variety of immune cell functions. We determined the ability of SP-A derived from normal and asthmatic subjects to modulate the inflammatory response elicited by Mycoplasma pneumoniae, a pathogen known to exacerbate asthma. Fourteen asthmatic and ten normal control subjects underwent bronchoscopy with airway brushing and bronchoalveolar lavage (BAL). Total SP-A was extracted from BAL. The ratio of SP-A1/total SP-A and the binding of total SP-A to M. pneumoniae membranes were determined. Airway epithelial cells from subjects were exposed to either normal or asthmatic SP-A before exposure to M. pneumoniae. IL-8 p... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5103967 Thu, 21 Jul 2011 23:00:00 +0100 5103967 http://www.medworm.com/index.php?rid=5103966&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21784969%26dopt%3DAbstract In conclusion, specific PDE4 inhibitors, such as NCS 613, may represent an alternative and isoform-specific approach toward reducing human lung inflammation and airway over reactivity. PMID: 21784969 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5103966 Thu, 21 Jul 2011 23:00:00 +0100 5103966 http://www.medworm.com/index.php?rid=5103965&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21784970%26dopt%3DAbstract In this study, we identified functionally important transcription factor binding sites in the TTF-1 proximal promoter and studied tumor necrosis factor-α (TNF-α) regulation of TTF-1 expression. TNF-α, a pro-inflammatory cytokine, has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) and inhibits surfactant protein levels. Deletion analysis of TTF-1 5'-flanking DNA indicated that the TTF-1 proximal promoter retained high level activity. Electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP) and mutational analysis experiments identified functional ZBP-89, Sp1, Sp3, and TTF-1 sites in the TTF-1 proximal promoter. TNF-α inhibited TTF-1 protein levels in H441 and primary alveolar type II cells. TNF-α inhibited TTF-1 gene transcrip... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5103965 Thu, 21 Jul 2011 23:00:00 +0100 5103965 http://www.medworm.com/index.php?rid=5058065&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21764986%26dopt%3DAbstract We examined Rab38 function in regulating lamellar body (LB) morphology in ATII cells. Quantitative electron microscopy revealed that LBs in ATII cells of the Rab38-null fawn-hooded hypertension (FHH) were ~77% larger than those in the control Sprague-Dawley rats. Rab38 protein expression was restricted in lung epithelial cells, but was not found in primary endothelial cells. In SD ATII cells, Rab38 protein level gradually declined during a five-day culture period. Importantly, endogenous Rab38 was present in LB fractions purified from SD rat lungs, and transiently expressed EGFP-Rab38 labeled only the limiting membranes of a sub-population of LBs in cultured ATII cells. This selective targeting was abolished by point mutations to EGFP-Rab38, and was not shared by Rab7 and Rab4b also functi... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5058065 Thu, 14 Jul 2011 23:00:00 +0100 5058065 http://www.medworm.com/index.php?rid=5058064&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21764987%26dopt%3DAbstract This study thus demonstrated that H(2) treatment is valuable for protection against irradiation lung damage with no known toxicity. PMID: 21764987 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5058064 Thu, 14 Jul 2011 23:00:00 +0100 5058064 http://www.medworm.com/index.php?rid=5058063&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21764988%26dopt%3DAbstract Authors: Zhou W, Dowell DR, Geraci MW, Blackwell TS, Collins RD, Polosukhin VV, Lawson WE, Wu P, Sussan TE, Biswal S, Goleniewska K, O'Neal J, Newcomb DC, Toki S, Morrow JD, Peebles RS The mortality rate for acute lung injury (ALI) is reported to be between 35-40% and there are very few treatment strategies that improve the death rate from this condition. Previous studies have suggested that signaling through the prostaglandin (PG) I(2) receptor may protect against bleomycin-induced ALI in mice. We found that mice that over-express PGI synthase (PGIS) in the airway epithelium were significantly protected against bleomycin-induced mortality and had reduced parenchymal consolidation, apoptosis of lung tissue, and generation of F(2)-isoprostanes compared to littermate wild type controls. ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5058063 Thu, 14 Jul 2011 23:00:00 +0100 5058063 http://www.medworm.com/index.php?rid=5058073&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21743024%26dopt%3DAbstract Authors: Farkas L, Farkas D, Warburton D, Gauldie J, Shi W, Stampfli MR, Voelkel NF, Kolb MR The concept of genetic susceptibility factors predisposing cigarette smokers to develop emphysema stems from the clinical observation that only a fraction of smokers develop clinically significant chronic obstructive pulmonary disease. We investigated whether Smad3 knockout mice, which develop spontaneous airspace enlargement after birth due to a defect in transforming growth factor (TGF)-β signaling, develop enhanced alveolar cell apoptosis and airspace enlargement following cigarette smoke exposure. We investigated Smad3(-/-) and Smad3(+/+) mice at different adult ages and determined airspace enlargement, alveolar cell proliferation and apoptosis. Furthermore, laser-capture microdissection a... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5058073 Thu, 07 Jul 2011 23:00:00 +0100 5058073 http://www.medworm.com/index.php?rid=5058072&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21743025%26dopt%3DAbstract Authors: van den Berg E, van Woensel JB, Bos AP, Bem RA, Altemeier WA, Gill SE, Martin TR, Matute-Bello G Infection with respiratory syncytial virus (RSV) in children can progress to respiratory distress and acute lung injury (ALI) necessitating mechanical ventilation (MV). MV enhances apoptosis and inflammation in mice infected with pneumonia virus of mice (PVM), a mouse pneumovirus that has been used as a model for severe RSV infection in mice. We hypothesized that the Fas/Fas ligand (FasL) system, a dual pro-apoptotic/pro-inflammatory system involved in other forms of lung injury, is required for enhanced lung injury in mechanically-ventilated mice infected with PVM. C57BL/6 mice and Fas-deficient ("lpr") mice were inoculated intratracheally with PVM. Seven or eight days after PVM i... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5058072 Thu, 07 Jul 2011 23:00:00 +0100 5058072 http://www.medworm.com/index.php?rid=5058071&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21743026%26dopt%3DAbstract Authors: Wright C, Pilkington R, Callaghan M, McClean S Burkholderia cepacia complex is a group of bacterial pathogens which cause opportunistic infections in cystic fibrosis (CF). The most virulent of these is Burkholderia cenocepacia. Matrix metalloproteases (MMPs) are upregulated in CF patients. The aim of this work was to examine the role of MMPs in the pathogenesis of B. cepacia complex, which has not been explored to date. Real-time PCR analysis showed that B. cenocepacia infection up-regulated MMP-2 and MMP-9 genes in CF lung cell line, CFBE41o- within 1 h; while MMP-2, -7 and -9 genes were up-regulated in non-CF lung cell line, 16HBE14o-. Conditioned media from both cell lines showed increased MMP-9 activation following B. cenocepacia infection. Conditioned media from B. cenoce... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5058071 Thu, 07 Jul 2011 23:00:00 +0100 5058071 http://www.medworm.com/index.php?rid=5058070&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21743027%26dopt%3DAbstract Authors: Zamjahn JB, Quinton LJ, Mack JC, Frevert CW, Nelson S, Bagby GJ Previously we showed that cytokine-induced neutrophil chemoattractant (CINC), but not macrophage inflammatory protein-2 (MIP-2), is detected in plasma after intratracheal challenge with lipopolysaccharide (LPS) or the particular chemokines. To further understand the differences between CINC and MIP-2 flux from the lung, we attempted to detect the two chemokines in isolated erythrocytes and leukocytes in rats after intratracheal LPS challenge. In response to intratracheal LPS, we found both CINC and MIP-2 in isolated erythrocytes and leukocytes suggesting that MIP-2 produced in the LPS challenged lung entered the circulation like CINC. To assess the relative flux of CINC and MIP-2 from the intraalveolar compartment... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5058070 Thu, 07 Jul 2011 23:00:00 +0100 5058070 http://www.medworm.com/index.php?rid=5058069&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21743028%26dopt%3DAbstract ENHANCEMENT OF ALVEOLAR EPITHELIAL SODIUM CHANNEL ACTIVITY WITH DECREASED CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR EXPRESSION IN MOUSE LUNG. Am J Physiol Lung Cell Mol Physiol. 2011 Jul 8; Authors: Lazrak A, Jurkuvenaite A, Chen L, Keeling KM, Collawn JF, Bedwell DM, Matalon S We sought to establish whether the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) regulates the activity of amiloride sensitive sodium channels (ENaC) in alveolar epithelial cells of wild type, heterozygous (Cftr (+/-)), knockout (Cftr (-/-)) and ΔF508 expressing mice in situ. RT-PCR studies confirmed the presence of CFTR message in freshly isolated ATII cells from wild type mice. We patched alveolar type I (ATI) and type II (ATII) cells in freshly prepared lung slices from these m... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5058069 Thu, 07 Jul 2011 23:00:00 +0100 5058069 http://www.medworm.com/index.php?rid=5058068&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21743029%26dopt%3DAbstract This study demonstrates that TROP2 is a likely regulator of fetal lung cell proliferation during development. PMID: 21743029 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5058068 Thu, 07 Jul 2011 23:00:00 +0100 5058068 http://www.medworm.com/index.php?rid=5058067&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21743030%26dopt%3DAbstract Authors: Redente EF, Jacobsen KM, Solomon JJ, Lara AR, Faubel S, Keith RC, Henson PM, Downey GP, Riches DW Fibrotic interstitial pneumonias are more prevalent in males of advancing age though little is known about the underlying mechanisms. To evaluate the contributions of age and gender to the development of pulmonary fibrosis, we intratracheally instilled young (8-12 weeks) and aged (52-54 weeks) male and female mice with bleomycin and assessed the development and severity of fibrotic lung disease by measurements of lung collagen levels, static compliance, leukocyte infiltration and stereologic quantification of fibrotic areas in histologic sections. We also quantified pro-inflammatory and pro-fibrotic chemokine and cytokine levels in the bronchoalveolar lavage fluid (BALF). Aged mal... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5058067 Thu, 07 Jul 2011 23:00:00 +0100 5058067 http://www.medworm.com/index.php?rid=5058066&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21743031%26dopt%3DAbstract In conclusion, VILI can be reverted by normalizing ventilation pressures. An adequate inflammatory response and extracellular matrix remodeling are essential for recovery. MMP-2 could play a key role in epithelial repair after VILI and ARDS. PMID: 21743031 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=5058066 Thu, 07 Jul 2011 23:00:00 +0100 5058066 http://www.medworm.com/index.php?rid=4961735&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21685241%26dopt%3DAbstract Authors: Lund AK, Lucero J, Herbert L, Liu Y, Naik JS Human immunodeficiency virus-associated pulmonary arterial hypertension (HIV-PAH) is a serious noninfectious disease involving an aberrant increase in pressure in the blood vessels of the lung, which leads to right ventricular (RV) heart failure and can eventually result in death. There is a current lack of viable animal models of HIV-PAH that has limited the identification of signaling pathways involved in HIV-mediated onset and progression of PAH. To determine whether the HIV-1 transgenic (HIV Tg) rat displays pathophysiological endpoints associated with PAH, we evaluated right ventricle peak systolic pressure (RVSP), right ventricular hypertrophy, pulmonary vessel remodeling and alterations in gene expression by real time PCR and... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=4961735 Thu, 16 Jun 2011 23:00:00 +0100 4961735 http://www.medworm.com/index.php?rid=4961734&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21685242%26dopt%3DAbstract Authors: Jiang J, George SC Exhaled nitric oxide (eNO) is a potential non-invasive biomarker of inflammation in asthma. The significant intersubject variability of eNO within clinically similar patients has contributed to its limited clinical application. Arginase and NO synthase (NOS) utilize the same substrate (L-arginine), and contribute to the fibrotic and inflammatory features of asthma, respectively. Interestingly, TGF-β2 can increase the expression of arginase, stimulates fibrosis, and is overexpressed in asthma. We hypothesized that TGF-β2-enhanced arginase activity would decrease gas phase NO release from lung epithelial cells by limiting L-arginine availability for NOS. Our results show that TGF-β2 (5 ng/ml) significantly enhances total arginase activity up to 2-3 fold in ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=4961734 Thu, 16 Jun 2011 23:00:00 +0100 4961734 http://www.medworm.com/index.php?rid=4961733&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21685243%26dopt%3DAbstract Authors: Kuebler WM not applicable. PMID: 21685243 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=4961733 Thu, 16 Jun 2011 23:00:00 +0100 4961733 http://www.medworm.com/index.php?rid=4912747&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21642449%26dopt%3DAbstract Authors: Desai LP, Wu Y, Tepper RS, Gunst SJ Airway smooth muscle phenotype may be modulated in response to external stimuli under physiologic and pathophysiologic conditions. The effect of mechanical forces on airway smooth muscle phenotype were evaluated in vitro by suspending weights of 0.5 gm or 1 gm from the ends of canine tracheal smooth muscle tissues, incubating the weighted tissues for six hours, and then measuring the expression of the phenotypic marker protein, smooth muscle myosin heavy chain (SmMHC). Incubation of the tissues at a High Load significantly increased expression of SmMHC as compared to incubation at Low Load. Incubation of the tissues at a High Load also decreased activation of PKB/Akt, as indicated by its phosphorylation at Ser 473. Inhibition of Akt or PI3 k... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=4912747 Thu, 02 Jun 2011 23:00:00 +0100 4912747 http://www.medworm.com/index.php?rid=4865981&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21602446%26dopt%3DAbstract Authors: Gwinn WM, Kapita MC, Wang PM, Cesta MF, Martin WJ Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by a progressive, irreversible and ultimately lethal form of lung fibrosis. Except for lung transplantation, no effective treatment options currently exist. The bleomycin animal model is one of the best studied models of lung injury and fibrosis. A previous study using mouse tumor models observed that liposome-encapsulated bleomycin exhibited reduced lung toxicity. Therefore, we hypothesized that airway-delivery of synthetic phosphatidylcholine-containing liposomes alone would protect mice from bleomycin-induced lung toxicity. C57BL/6 mice were administered uncharged multilamellar liposomes (100 µl) or PBS vehicle on day 0 by airway delivery. Bleomycin ... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=4865981 Thu, 19 May 2011 23:00:00 +0100 4865981 http://www.medworm.com/index.php?rid=4813902&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21551081%26dopt%3DAbstract Authors: Clerici C no abstract. PMID: 21551081 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology) American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=4813902 Thu, 05 May 2011 23:00:00 +0100 4813902 http://www.medworm.com/index.php?rid=4813906&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531774%26dopt%3DAbstract Authors: Sears PR, Davis CW, Chua M, Sheehan JK The airway epithelial surface liquid is generally considered to be composed of two layers---a periciliary layer and a continuous thick mucus layer moving in bulk. This view may not be appropriate for all areas of the lung. Our hypothesis, that mucus may form a discontinuous layer with dynamic attachments to the surface, is investigated using a culture system. We investigated thin mucus layers using live-cell confocal microscopy and fluorescent beads and exogenous MUC5B to visualize mucus dynamics on ciliated human bronchial cultures. A continuous mucus layer was never observed. In sparsely ciliated cultures mucus attached to ciliated cells, but in highly ciliated cultures mucus formed strands several hundred micrometers long. As with incr... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=4813906 Thu, 28 Apr 2011 23:00:00 +0100 4813906 http://www.medworm.com/index.php?rid=4813905&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531775%26dopt%3DAbstract In this study, we used both in vitro and in vivo models to demonstrate the robust inductions of mucin production by V(2)O(5). Furthermore, the follow-up mechanistic study revealed a novel RAF1-IKK-NF-κB pathway that mediated V(2)O(5)-induced mucin production. Most interestingly, the reactive oxygen species (ROS) and the classical mucin-inducing EGFR-MAPK pathway appeared not to be involved in this process. Thus, the V2O5-induced mucin production may represent a novel EGFR-MAPK independent and environmental toxicant associated MO model. Complete elucidation of the signaling pathway in this model will not only facilitate the development of the treatment for V(2)O(5) associated occupational diseases, but also advance our understanding on the EGFR-independent mucin production in other chronic... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=4813905 Thu, 28 Apr 2011 23:00:00 +0100 4813905 http://www.medworm.com/index.php?rid=4813904&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531776%26dopt%3DAbstract Authors: Garg P, Yang S, Liu A, Pallero MA, Buchsbaum DJ, Mosher DF, Murphy-Ullrich JE, Goldblum SE Thrombospondin (TSP)-1 is a multidomain protein that contains epidermal growth factor (EGF)-like repeats that indirectly activate the EGF receptor (EGFR) and selected downstream signaling pathways. In these studies, we show that TSP1 opens the paracellular pathway in a human lung microvascular endothelial cell (HMVEC-L)s in a dose-, time-, and protein tyrosine kinase (PTK)-dependent manner. TSP1 increased tyrosine phosphorylation of proteins enriched to intercellular boundaries including the zonula adherens (ZA) proteins, vascular endothelial (VE)-cadherin, γ-catenin, and p120 catenin. In HMVEC-Ls, EGFR and ErbB2 are expressed at low levels, and both heterodimerize and tyrosine autophos... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=4813904 Thu, 28 Apr 2011 23:00:00 +0100 4813904 http://www.medworm.com/index.php?rid=4813903&cid=s_37403_171_f&fid=37403&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531777%26dopt%3DAbstract Authors: Nicola T, Ambalavanan N, Zhang W, James ML, Rehan VK, Halloran BA, Olave N, Bulger A, Oparil S, Chen YF Hypoxia enhances transforming growth factor-beta (TGF-β) signaling, inhibiting alveolar development and causing abnormal pulmonary arterial remodeling in the newborn lung. We hypothesized that during chronic hypoxia, reduced peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling may contribute to, or be caused by excessive TGF-β signaling. To determine if PPAR-γ was reduced during hypoxia, C57BL/6 mice were exposed to hypoxia from birth to two weeks and evaluated for PPAR-γ mRNA and protein. To determine if rosiglitazone (RGZ, a PPAR-γ agonist) supplementation attenuated the effects of hypoxia, mice were exposed to air or hypoxia from birth to two weeks in... American Journal of Physiology. Lung Cellular and Molecular Physiology journals http://www.medworm.com/rss/comments.php?id=4813903 Thu, 28 Apr 2011 23:00:00 +0100 4813903