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 Respiratory Cell and Molecular Biology' source. Thu, 09 Feb 2012 16:56:36 +0100 http://www.medworm.com/index.php?rid=5639403&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22281984%26dopt%3DAbstract Authors: Medina JL, Coalson JJ, Brooks EG, Winter VT, Chaparro A, Principe MF, Kannan TR, Baseman JB, Dube PH Abstract Mycoplasma pneumoniae causes acute and chronic lung infections in humans leading to a variety of pulmonary and extra-pulmonary sequelae. Of the airway complications of M. pneumoniae infection, M. pneumoniae-associated exacerbation of asthma and pediatric wheezing are emerging as significant sources of human morbidity. However, M. pneumoniae products capable of promoting allergic inflammation are unknown. Recently, we reported that M. pneumoniae produces an ADP-ribosylating and vacuolating toxin termed the CARDS toxin. Here we report that naïve mice exposed to a single dose of recombinant CARDS (rCARDS) toxin respond with a robust inflammatory response consistent w... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5639403 Thu, 26 Jan 2012 05:00:00 +0100 5639403 http://www.medworm.com/index.php?rid=5639402&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22281985%26dopt%3DAbstract Conclusions: Taken together, the above results show that CCL-2 is functionally important in the down modulation of injury and inflammation in LC. PMID: 22281985 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5639402 Thu, 26 Jan 2012 05:00:00 +0100 5639402 http://www.medworm.com/index.php?rid=5639401&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22281986%26dopt%3DAbstract Authors: Tulapurkar ME, Almutairy EA, Shah NG, He JR, Puche AC, Shapiro P, Singh IS, Hasday JD Abstract Acute Respiratory Distress Syndrome (ARDS) is a neutrophil (PMN)-driven lung injury that is associated with fever and heat-stroke and has ~40% mortality. In mouse models of acute lung injury (ALI), febrile-range hyperthermia (FRH) enhanced PMN accumulation, vascular permeability, and epithelial injury, in part by augmenting pulmonary CXC chemokine expression. To determine whether FRH increases chemokine responsiveness within the lung, we utilized in vivo and in vitro models that bypass endogenous chemokine generation. We measured PMN transalveolar migration (TAM) in mice after intratracheal instillation of the human CXC chemokine IL-8 in vivo and IL-8-directed PMN transendothelia... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5639401 Thu, 26 Jan 2012 05:00:00 +0100 5639401 http://www.medworm.com/index.php?rid=5639400&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22281987%26dopt%3DAbstract Authors: Bae HB, Zmijewski JW, Deshane JS, Zhi D, Thompson LC, Peterson CB, Chaplin DD, Abraham E Abstract Vitronectin is present in large concentrations in serum and the extracellular matrix. While vitronectin is known to modulate neutrophil adhesion and chemotaxis, and to contribute to neutrophil associated proinflammatory processes, a role in apoptosis has not been demonstrated. In the present studies, we found that neutrophils demonstrated more rapid progression to spontaneous or TRAIL induced apoptosis when incubated under vitronectin free conditions than when vitronectin was present. The ability of native vitronectin to delay neutrophil apoptosis was not recapitulated by the vitronectin somatomedin B (SMB) domain. In contrast, inclusion of the RGDfv peptide in cultures contai... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5639400 Thu, 26 Jan 2012 05:00:00 +0100 5639400 http://www.medworm.com/index.php?rid=5639399&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22281988%26dopt%3DAbstract Authors: Yang Z, Balenga N, Cooper PR, Damera G, Edwards R, Brightling CE, Panettieri Jr RA, Druey KM Abstract Severe asthma is associated with fixed airway obstruction due to inflammation, copious luminal mucous, and increased airway smooth muscle (ASM) mass. Paradoxically, studies have demonstrated that hypertrophic and hyperplastic ASM characteristic of severe asthma has reduced contractile capacity. We compared GPCR-induced Ca(2+) mobilization and expression of GPCRs and signaling proteins related to procontractile signaling in ASM derived post-mortem from subjects who died of non-respiratory causes to cells from subjects who died of asthma. Despite increased or comparable expression of contraction-promoting GPCRs (bradykinin B2 or histamine H1 and PAR1, respectively) in asthma... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5639399 Thu, 26 Jan 2012 05:00:00 +0100 5639399 http://www.medworm.com/index.php?rid=5639407&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22268139%26dopt%3DAbstract Conclusion: We conclude that, in human pulmonary fibroblasts, TGF-β acts on ryanodine-sensitive channels, leading to Ca(2+) wave activity, which in turn amplifies extracellular matrix gene expression. PMID: 22268139 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5639407 Fri, 20 Jan 2012 05:00:00 +0100 5639407 http://www.medworm.com/index.php?rid=5639406&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22268140%26dopt%3DAbstract Authors: Varisco BM, Ambalavanan N, Whitsett JA, Hagood JS Abstract Thy-1 is a glycosylphosphytidylinositol linked cell surface glycoprotein present on a subset of lung fibroblasts that has an important role in postnatal alveolarization. In the present study, we define the role of Thy-1 in pulmonary lipofibroblast differentiation and in the regulation of lipid homeostasis via Peroxisome Proliferator-Activated Receptor-γ (PPARγ). Thy-1 was associated with interstitial cells containing lipid droplets in vivo. Transfection of Thy-1 into Thy-1 (-) fibroblasts increased triglyceride content, fatty acid uptake, and the expression of the lipofibroblast marker adipocyte differentiation related protein (ADRP). Thy-1 (+) fibroblasts exhibited 2.4 fold higher PPARγ activity, and inhibitio... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5639406 Fri, 20 Jan 2012 05:00:00 +0100 5639406 http://www.medworm.com/index.php?rid=5639405&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22268141%26dopt%3DAbstract Conclusions. PlGF and its receptor VEGFR1 are up-regulated in allergic asthma and play a pro-inflammatory role by inducing tissue edema, increasing tissue neutrophilia and IL-17 production. PMID: 22268141 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5639405 Fri, 20 Jan 2012 05:00:00 +0100 5639405 http://www.medworm.com/index.php?rid=5639404&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22268142%26dopt%3DAbstract Authors: Suzuki Y, Suda T, Furuhashi K, Shibata K, Hashimoto D, Enomto N, Fujisawa T, Nakamura Y, Inui N, Nakamura H, Chida K Abstract Lung dendritic cells (LDC) are primary antigen-presenting cells that develop IgA-producing plasma cells in the lung through class switch recombination (CSR) in naïve B cells. Recently, it was found that the major LDC subsets comprise of CD103(-)CD11b(high)LDC (CD11b(high) LDC) and CD103(+)CD11b(low or negative)LDC (CD103(+) LDC), but their abilities to induce IgA production have not been defined. Under T cell-dependent (T-D) and T cell-independent (TI-D) conditions, we compared the abilities of these two LDC populations to induce IgA. CD11b(high) or CD103(+) LDC obtained from BALB/c mice were cocultured with naïve IgD(+) B cells in the presence of... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5639404 Fri, 20 Jan 2012 05:00:00 +0100 5639404 http://www.medworm.com/index.php?rid=5599891&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22246860%26dopt%3DAbstract Authors: Vadász I, Hubmayr RD, Nin N, Sporn PH, Sznajder JI Abstract Patients with severe acute and chronic lung diseases develop derangements in gas exchange that may result in increased levels of CO(2) (hypercapnia), the effects of which on human health are incompletely understood. It has been proposed that hypercapnia may have beneficial effects in patients with acute lung injury, and the concepts of "permissive" and even "therapeutic" hypercapnia have emerged. However, recent work suggests that CO(2) can act as a signaling molecule via pH-independent mechanisms, resulting in deleterious effects in the lung. Here we review recent research on how elevated CO(2) is sensed by cells in the lung and the potential harmful effects of hypercapnia on epithelial and endothelial barrier, ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5599891 Thu, 12 Jan 2012 05:00:00 +0100 5599891 http://www.medworm.com/index.php?rid=5599890&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22246861%26dopt%3DAbstract Authors: Munitz A, Cole ET, Atar-Karo D, Finkelman FD, Rothenberg ME Abstract Resistin-like molecule alpha (Relm-α) is one of the most up-regulated gene products in allergen and parasite-associated Th2 responses. Localized to alternatively activated macrophages, Relm-α has been shown to have an anti-inflammatory effect in parasite-induced Th2 responses, but its role in experimental asthma remains unexplored. Herein, we analyzed the cellular source, IL-4 receptors required to stimulate Relm-α production, and the role of Relm-α following experimental asthma induction by IL-4, IL-13 or multiple experimental regimes, including OVA and Aspergillus fumigatus immunization. We demonstrate that Relm-α was secreted into the airway lumen, dependent upon both IL-13Rα1 and likely the type... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5599890 Thu, 12 Jan 2012 05:00:00 +0100 5599890 http://www.medworm.com/index.php?rid=5599889&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22246862%26dopt%3DAbstract Conclusions: These observations provide a unified mechanism of how maternal smoking during pregnancy may lead to lifelong alterations in offspring pulmonary function and increased risk of asthma, and suggests potential targets to counteract those effects. PMID: 22246862 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5599889 Thu, 12 Jan 2012 05:00:00 +0100 5599889 http://www.medworm.com/index.php?rid=5599888&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22246863%26dopt%3DAbstract Authors: Uchida M, Shiraishi H, Ohta S, Arima K, Taniguchi K, Suzuki S, Okamoto M, Ahlfeld SK, Ohshima K, Kato S, Toda S, Sagara H, Aizawa H, Hoshino T, Conway SJ, Hayashi S, Izuhara K Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and usually fatal form of interstitial lung disease (ILD). The precise molecular mechanisms of IPF remain poorly understood; however, analyses of bleomycin (BLM)-administered mice as a model of IPF have established the importance of preceding inflammation for the formation of fibrosis. Periostin is a recently characterized matricellular protein involved in modulating cell functions. We have recently found that periostin is highly expressed in the lung tissues of IPF patients, suggesting that it may play a role in the process of p... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5599888 Thu, 12 Jan 2012 05:00:00 +0100 5599888 http://www.medworm.com/index.php?rid=5599887&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22246864%26dopt%3DAbstract Authors: Davies ER, Haitchi HM, Thatcher TH, Sime PJ, Kottmann RM, Ganesan A, Packham G, O'Reilly KM, Davies DE Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disorder characterized by the proliferation of interstitial fibroblasts and deposition of extracellular matrix causing impaired gas exchange. Spiruchostatin A (SpA) is an histone deacetylase inhibitor (HDI) with selectivity towards class I enzymes which distinguishes it from other non-specific HDIs which are reported to inhibit (myo)fibroblast proliferation and differentiation. As the selectivity of HDIs may be important clinically, we postulated that SpA inhibits proliferation and differentiation of IPF fibroblasts. Primary fibroblasts were grown from lung biopsy explants obtained from patients with I... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5599887 Thu, 12 Jan 2012 05:00:00 +0100 5599887 http://www.medworm.com/index.php?rid=5578142&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227561%26dopt%3DAbstract In this study, we hypothesized that TGF-β also affects ADAM33 expression in bronchial fibroblasts in asthma. Primary fibroblasts were grown from bronchial biopsies from normal and asthmatic donors and treated with TGF-β(2) to induce myofibroblast differentiation. ADAM33 expression was assessed using quantitative RT-PCR and Western blotting. To examine the mechanisms whereby TGF-β(2) affected ADAM33 expression, quantitative methylation-sensitive PCR, chromatin immunoprecipitation and nuclear accessibility assays were conducted on the ADAM33 promoter. We found that TGF-β(2) caused a time- and concentration-dependent reduction in ADAM33 mRNA expression in normal and asthmatic fibroblasts, affecting levels of splice variants similarly. TGF-β(2) also induced ADAM33 protein turnover and app... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5578142 Fri, 06 Jan 2012 05:00:00 +0100 5578142 http://www.medworm.com/index.php?rid=5578141&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227562%26dopt%3DAbstract Authors: Bhandari V, Choo-Wing R, Harijith A, Sun H, Syed MA, Homer RJ, Elias JA Abstract Supplemental oxygen is frequently prescribed. However, prolonged exposure to high concentrations of oxygen causes hyperoxic acute lung injury (HALI) which manifests as acute respiratory distress syndrome in adults and leads to bronchopulmonary dysplasia in newborns. Nitric oxide (NO), nitric oxide synthases (NOS) and Angiopoietin 2 (Ang2) have been implicated in the pathogenesis of HALI. However, the mechanisms of the contributions of NOS/NO and the relationship(s) between NOS/NO and Ang2 have not been addressed. In addition, the relevance of these moieties in adults and newborns has not been evaluated. To address these issues, we compared the responses in hyperoxia of wild type (NOS (+/+)) an... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5578141 Fri, 06 Jan 2012 05:00:00 +0100 5578141 http://www.medworm.com/index.php?rid=5578140&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227563%26dopt%3DAbstract Authors: Torres-González E, Bueno M, Tanaka A, Krug LT, Cheng DS, Polosukhin VV, Sorescu D, Lawson WE, Blackwel TS, Rojas M, Mora AL Abstract The incidence of Idiopathic pulmonary fibrosis (IPF) increases with age. The mechanisms that underlie the age-dependent risk for IPF are unknown. Based on studies that suggest an association of IPF and gammaherpesvirus infection, we infected young (2-3 mo) and old (≥18 mo) C57BL/6 mice with the murine gammaherpesvirus 68 (MHV68). Acute MHV68 infection in aging mice resulted in severe pneumonitis and fibrosis compared with young animals. Progressive clinical deterioration and lung fibrosis in the late chronic phase of infection was observed exclusively in old mice with diminution of tidal volume. Infected aging mice showed higher expression... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5578140 Fri, 06 Jan 2012 05:00:00 +0100 5578140 http://www.medworm.com/index.php?rid=5560036&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210825%26dopt%3DAbstract Authors: Goncharova EA, Goncharov DA, Zhao H, Penn RB, Krymskaya VP, Panettieri RA Abstract Severe asthma manifests as airway remodeling and irreversible airway obstruction, in part because of the proliferation and migration of human airway smooth muscle (HASM) cells. We previously reported that cyclic adenosine monophosphate-mobilizing agents, including β(2)-adrenergic receptor (β(2)AR) agonists, which are mainstay of asthma therapy, and prostaglandin E2 (PGE2), inhibit the migration of HASM cells, although the mechanism for this migration remains unknown. Vasodilator-stimulated phosphoprotein (VASP), an anticapping protein, modulates the formation of actin stress fibers during cell motility, and is negatively regulated by protein kinase A (PKA)-specific inhibitory phosphorylati... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5560036 Sun, 01 Jan 2012 05:00:00 +0100 5560036 http://www.medworm.com/index.php?rid=5560035&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210826%26dopt%3DAbstract Authors: Ghio AJ, Soukup JM, Dailey LA, Richards JH, Turi JL, Pavlisko EN, Roggli VL Abstract The mechanism for biological effects after exposure to particles is incompletely understood. One postulate proposed to explain biological effects after exposure to particles involves altered iron homeostasis in the host. The fibro-inflammatory properties of mineral oxide particles are exploited therapeutically with the instillation of massive quantities of talc into the pleural space, to provide sclerosis. We tested the postulates that (1) in vitro exposure to talc induces a disruption in iron homeostasis, oxidative stress, and a biological effect, and (2) talc pleurodesis in humans alters iron homeostasis. In vitro exposures of both mesothelial and airway epithelial cells to 100 μg/ml ta... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5560035 Sun, 01 Jan 2012 05:00:00 +0100 5560035 http://www.medworm.com/index.php?rid=5560034&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210827%26dopt%3DAbstract Authors: PMID: 22210827 [PubMed - in process] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5560034 Sun, 01 Jan 2012 05:00:00 +0100 5560034 http://www.medworm.com/index.php?rid=5534464&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22095627%26dopt%3DAbstract Authors: Tanaka A, Jin Y, Lee SJ, Zhang M, Kim HP, Stolz DB, Ryter SW, Choi AM Abstract Epithelial cell death plays a critical role in hyperoxia-induced lung injury. We investigated the involvement of the autophagic marker microtubule-associated protein-1 light chain-3B (LC3B) in epithelial apoptosis after hyperoxia. Prolonged hyperoxia (>95% O2), which causes characteristic lung injury in mice, activated morphological and biochemical markers of autophagy. Hyperoxia induced the time-dependent expression and conversion of LC3B-I to LC3B-II in mouse lung in vivo and in cultured epithelial cells (Beas-2B, HBE) in vitro. Hyperoxia increased autophagosome formation in Beas-2B cells as evidenced by electron microscopy and increased GFP-LC3 puncta. The augmented LC3B level after hyper... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5534464 Thu, 17 Nov 2011 05:00:00 +0100 5534464 http://www.medworm.com/index.php?rid=5534463&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22095628%26dopt%3DAbstract Authors: Niu K, Asada M, Okazaki T, Yamanda S, Ebihara T, Guo H, Zhang D, Nagatomi R, Arai H, Kohzuki M, Ebihara S Abstract Malignant mesothelioma (MM) is caused by exposure to asbestos. Because MM has a latency period, short survival time, and has a poor response to current therapeutic regimes, long-term preventive strategies are required to suppress the advance of pathological states after asbestos exposure. Accumulating evidences suggest that adiponectin plays a crucial role in the regulation of energy metabolism by increasing AMP-activated protein kinase (AMPK) activation. Several studies have indicated that the activation of AMPK decreases cyclooxygenase-2 (COX-2) expression. Since high COX-2 levels correlated with a worse prognosis and survival rate in MM, we examined whether... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5534463 Thu, 17 Nov 2011 05:00:00 +0100 5534463 http://www.medworm.com/index.php?rid=5419844&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074702%26dopt%3DAbstract Conclusions: Inhibition of Pim1 kinase was effective in preventing the development of AHR, airway inflammation, and cytokine production in allergen sensitized and challenged mice. These data identify the important role of Pim1 kinase in the full development of allergen-induced airway responses. PMID: 22074702 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5419844 Thu, 10 Nov 2011 05:00:00 +0100 5419844 http://www.medworm.com/index.php?rid=5419843&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074703%26dopt%3DAbstract In this study we investigated the effects of CQ on growth, death and autophagic activity of malignant mesothelioma (MM) cell lines cultured in standard versus nutritional stress conditions partially mimicking those found in the tumor microenvironment. We report that in each cell line the toxic effects of CQ were amplified by nutritional stress and paralleled by autophagy inhibition. Still, the cell lines displayed different levels of sensitivity to CQ toxicity which did not correlate with their relative degrees of constitutive and nutritional stress-induced autophagy nor with the relative magnitude of the autophagy inhibition induced by the drug. Thus, we tested the hypothesis that the cell lines' sensitivity to CQ was related to their variable dependence on recycling of intracellular cons... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5419843 Thu, 10 Nov 2011 05:00:00 +0100 5419843 http://www.medworm.com/index.php?rid=5419848&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22052876%26dopt%3DAbstract Authors: Auten RL, Gilmour MI, Krantz QT, Potts EN, Mason SN, Foster WM Abstract Air pollutant exposure is linked with childhood asthma incidence and exacerbations, and maternal exposure to airborne pollutants during pregnancy increases airway hyperreactivity (AHR) in offspring. To determine if exposure to diesel exhaust during pregnancy worsened postnatal ozone-induced AHR, timed pregnant C57BL/6 mice were exposed to diesel exhaust (0.5 or 2.0 mg/m(3)) 4 h daily from gestation day (GD) 9 to 17, or received twice weekly oropharyngeal aspirations of the collected diesel exhaust particles (DEPs). Placentas and fetal lungs were harvested on gestation day 18 for cytokine analysis. In other litters, pups born to dams exposed to air or diesel exhaust, or to dams treated with aspirated d... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5419848 Thu, 03 Nov 2011 04:00:00 +0100 5419848 http://www.medworm.com/index.php?rid=5419847&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22052877%26dopt%3DAbstract In this report we demonstrate that POPG acts as a strong anti-viral agent against IAV. POPG markedly attenuated IL-8 production and cell death induced by IAV in cultured human bronchial epithelial cells. The lipid also suppressed viral attachment to the plasma membrane and subsequent replication in MDCK cells. Two virus strains, H1N1-PR8-IAV and H3N2-IAV bind to POPG with high affinity but exhibit only low affinity interactions with the structurally related lipid palmitoyl-oleoyl-phosphatidylcholine. Intranasal inoculation of H1N1-PR8-IAV in mice, in the presence of POPG, markedly suppressed the development of inflammatory cell infiltrates and the induction of IFN-γ recovered in bronchoalveolar lavage, and viral titers recovered from the lungs after 5 days of infection. These findings ide... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5419847 Thu, 03 Nov 2011 04:00:00 +0100 5419847 http://www.medworm.com/index.php?rid=5419846&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22052878%26dopt%3DAbstract Conclusions. This is the first study to report highly significant inter-strain variation in hyperoxia-induced changes in minute ventilation, HR and HRV, and to identify polymorphisms in candidate susceptibility genes that associate with cardiac responses. Results indicate that changes in HR and LF HRV could be important predictors of subsequent adverse outcome during hyperoxia exposure, specifically the pathogenesis of acute lung injury. Understanding the genetic mechanisms of these responses may have significant diagnostic clinical value. PMID: 22052878 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5419846 Thu, 03 Nov 2011 04:00:00 +0100 5419846 http://www.medworm.com/index.php?rid=5419845&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22052879%26dopt%3DAbstract Conclusions: ASK-1 is an important regulator of lung injury and apoptosis in this model. Further study is needed to determine the mechanism of lung injury and apoptosis by ASK-1 and its downstream mediators in the lung. PMID: 22052879 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5419845 Thu, 03 Nov 2011 04:00:00 +0100 5419845 http://www.medworm.com/index.php?rid=5296996&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21980054%26dopt%3DAbstract Conclusions: CSE-induced oxidation of CKB is a trigger for proteasomal degradation. Concomitant loss of enzymatic activity regulating energy homeostasis may lead to the acceleration of bronchial epithelial cell senescence, which is implicated in the pathogenesis of COPD. PMID: 21980054 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5296996 Thu, 06 Oct 2011 04:00:00 +0100 5296996 http://www.medworm.com/index.php?rid=5296995&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21980055%26dopt%3DAbstract The objective of this study was twofold: 1) evaluate the impact of acute hyperglycemia on lung IR injury, and 2) determine if RAGE signaling is a mechanism of hyperglycemia-enhanced IR injury. We hypothesized that acute hyperglycemia worsens lung IR injury through a RAGE signaling mechanism. C57BL/6 wild-type (WT) and RAGE knockout (RAGE-/-) mice underwent sham thoracotomy or lung IR (1hr left hilar occlusion and 2hrs reperfusion). Acute hyperglycemia was established by dextrose injection 30 min prior to ischemia. Lung injury was assessed by measuring lung function, cytokine expression in bronchoalveolar lavage fluid, leukocyte infiltration, and microvascular permeability via Evans blue dye. Mean blood glucose levels doubled in hyperglycemic mice 30 min after dextrose injection. Compared t... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5296995 Thu, 06 Oct 2011 04:00:00 +0100 5296995 http://www.medworm.com/index.php?rid=5296994&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21980056%26dopt%3DAbstract Authors: Willner D, Haynes MR, Furlan M, Hanson N, Kirby B, Lim YW, Rainey PB, Schmieder R, Youle M, Conrad D, Rohwer F Abstract Microbial communities in the lungs of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) patients have been shown to be spatially heterogeneous. Viral communities may also vary spatially, leading to localized viral populations and infections. Here, we characterized viral communities from multiple areas of the lungs of two late-stage CF patients using metagenomics: the explanted lungs from transplant patient and lungs acquired post-mortem. All regions harbored eukaryotic viruses which may infect the human host, notably herpesviruses, anelloviruses, and papillomaviruses. In the highly diseased apical lobes of the explant lungs, viral dive... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5296994 Thu, 06 Oct 2011 04:00:00 +0100 5296994 http://www.medworm.com/index.php?rid=5297013&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21278324%26dopt%3DAbstract This study investigated the role of Toll-like receptor (TLR) 2, a pattern recognition receptor for gram-positive cell wall products, in regulating swine facility organic dust extract (DE)-induced airway inflammation in mice. Isolated lung macrophages from TLR2 knockout mice demonstrated reduced TNF-α, IL-6, keratinocyte chemoattractant/CXCL1, but not macrophage inflammatory protein-2/CXCL2 expression, after DE stimulation ex vivo. Next, using an established mouse model of intranasal inhalation challenge, we analyzed bronchoalveolar lavage fluid and lung tissue in TLR2-deficient and wild-type (WT) mice after single and repetitive DE challenge. Neutrophil influx and select cytokines/chemokines were significantly lower in TLR2-deficient mice at 5 and 24 hours after single DE challenge. After... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5297013 Sat, 01 Oct 2011 04:00:00 +0100 5297013 http://www.medworm.com/index.php?rid=5297012&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21278326%26dopt%3DAbstract We present evidence for a treprostinil/cAMP-induced downstream suppression of extracellular regulated kinase (ERK) that is transmitted via a protein kinase A-independent pathway through Rap proteins, which sequester Ras. The resulting dephosphorylated state of c-Raf limits the activity of ERK. The cell-matrix adhesion assay with the ERK inhibitor further confirmed that the adhesion of fibrocytes was impaired. Thus our data suggest that treprostinil inhibits the adhesion and differentiation of fibrocytes by limiting the activity of ERK via the cAMP-Rap axis. PMID: 21278326 [PubMed - in process] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5297012 Sat, 01 Oct 2011 04:00:00 +0100 5297012 http://www.medworm.com/index.php?rid=5297011&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21297077%26dopt%3DAbstract Authors: Maillet I, Schnyder-Candrian S, Couillin I, Quesniaux VF, Erard F, Moser R, Fleury S, Kanda A, Dombrowicz D, Szymkowski DE, Ryffel B Abstract Tumor Necrosis Factor (TNF) is a pleiotropic cytokine consisting of soluble and transmembrane forms, with distinct roles in inflammation and immunity. TNF is an important factor in allergic airway inflammation. However, the disparate functions of soluble (sol) and transmembrane (tm) TNF in lung pathology are not well understood. Our aim was to assess the activities of solTNF and tmTNF in murine models of allergic airway disease, and to evaluate the efficacy of solTNF-selective inhibition. We used ovalbumin sensitization and challenge of TNF knockout, tmTNF knockin, and wild-type C57BL/6 mice to distinguish differences in airway infla... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5297011 Sat, 01 Oct 2011 04:00:00 +0100 5297011 http://www.medworm.com/index.php?rid=5297010&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21317378%26dopt%3DAbstract Authors: Botelho FM, Llop-Guevara A, Trimble NJ, Nikota JK, Bauer CM, Lambert KN, Kianpour S, Jordana M, Stämpfli MR Abstract Although a similar prevalence of smoking is evident among patients with asthma and the general population, little is known about the impact of cigarette smoke on the immune inflammatory processes elicited by common environmental allergens. We investigated the impact of exposure to cigarette smoke on house dust mite (HDM)-induced allergic airway inflammation and its consequences for tissue remodeling and lung physiology in mice. BALB/c mice received intranasal HDMs daily, 5 days per week, for 3 weeks to establish chronic airway inflammation. Subsequently, mice were concurrently exposed to HDMs plus cigarette smoke, 5 days per week, for 2 weeks (HDMs + smoke)... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5297010 Sat, 01 Oct 2011 04:00:00 +0100 5297010 http://www.medworm.com/index.php?rid=5297009&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21317380%26dopt%3DAbstract Authors: Zscheppang K, Dörk T, Schmiedl A, Jones FE, Dammann CE Abstract Sufficient pulmonary surfactant production is required for the fetal-neonatal transition, especially in preterm infants. Neuregulin (NRG) and its transmembrane receptor ErbB4 positively regulate the onset of fetal surfactant synthesis. Details of this signaling process remain to be elucidated. ErbB4 is known to regulate gene expression in the mammary gland, where the receptor associates with the signal transducer and activator of transcription Stat5a to transactivate the β-casein gene promoter. We hypothesized that in the fetal lung, ErbB4 functions as a transcriptional regulator for surfactant protein B (Sftpb), the most critical surfactant protein gene. Re-expressing full-length ErbB4 in primary fetal ErbB... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5297009 Sat, 01 Oct 2011 04:00:00 +0100 5297009 http://www.medworm.com/index.php?rid=5297008&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21330464%26dopt%3DAbstract Authors: Tighe RM, Liang J, Liu N, Jung Y, Jiang D, Gunn MD, Noble PW Abstract The chemokine, CXCL10, and its cognate receptor, CXCR3, are important mediators of the pathobiology of lung fibrosis. Macrophages are a known source of CXCL10, but their specific source in the lung is poorly defined due to incomplete characterization of macrophage subpopulations. We recently developed a novel flow cytometric approach that discriminates resident alveolar macrophages from recruited exudative macrophages (ExMacs) after infectious lung injury. We hypothesized that ExMacs are present after noninfectious lung injury with bleomycin, and are a source of CXCL10. We found that ExMacs are recruited to the lung after injury, peaking at Day 7, then maintained through Day 28. ExMac recruitment was sig... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5297008 Sat, 01 Oct 2011 04:00:00 +0100 5297008 http://www.medworm.com/index.php?rid=5297007&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21330466%26dopt%3DAbstract In this study, the increased expression of NT4/5 and of its cognate receptor, the neurotrophic tyrosine kinase receptor Type 2 (TrkB), was observed in human lungs explanted from patients with idiopathic pulmonary fibrosis (IPF), and in lungs from mice with bleomycin-induced pulmonary fibrosis. The expression of NT4/5 and TrkB localized to hyperplastic alveolar Type II cells (ATII) and fibroblastic foci in affected lungs. Increased concentrations of NT4/5 and TrkB were evident in ATII isolated from the lungs of bleomycin-treated mice. Primary ATII were shown to secrete NT4/5 into the cell culture medium. The profibrotic cytokine transforming growth factor-β1, stimulated TrkB, but not NT4/5 gene expression, suggesting that perturbed profibrotic growth factor signaling in affected lungs may ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5297007 Sat, 01 Oct 2011 04:00:00 +0100 5297007 http://www.medworm.com/index.php?rid=5297005&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21378263%26dopt%3DAbstract This study of two different murine strains demonstrates that inflammation and airway hyperresponsiveness can be decoupled, and suggests that the down-modulation of expression of G-protein-coupled receptors involved in regulating airway smooth muscle contraction may contribute to this dissociation. PMID: 21378263 [PubMed - in process] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5297005 Sat, 01 Oct 2011 04:00:00 +0100 5297005 http://www.medworm.com/index.php?rid=5297004&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21421907%26dopt%3DAbstract Authors: Moore TV, Clay BS, Cannon JL, Histed A, Shilling RA, Sperling AI Abstract We and others reported that Inducible costimulator-deficient (ICOS(-/-)) mice manifest a defect in Th2-mediated airway inflammation, which was attributed to reduced Th2 differentiation in the absence of ICOS signaling. Interestingly, the number of CD4 T cells present in the airways and lungs after sensitization and challenge is significantly reduced in ICOS(-/-) mice. We now show that this reduction is not attributable simply to a reduced proliferation of ICOS(-/-) cells, because significantly more ICOS(-/-) than wild-type activated CD4 T cells are present in the lymph nodes, suggesting that more ICOS(-/-) CD4 T cells than wild-type CD4 T cells migrated into the lymph nodes. Further investigation rev... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5297004 Sat, 01 Oct 2011 04:00:00 +0100 5297004 http://www.medworm.com/index.php?rid=5297001&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21421908%26dopt%3DAbstract Authors: Waseda K, Miyahara N, Kanehiro A, Ikeda G, Koga H, Fuchimoto Y, Kurimoto E, Tanimoto Y, Kataoka M, Tanimoto M, Gelfand EW Abstract Most of the studies investigating the effectiveness of blocking the leukotriene B4 (LTB4) receptor 1 (BLT1) have been performed in models of primary or acute allergen challenge. The role of the LTB4-BLT1 pathway in secondary challenge models, where airway hyperresponsiveness (AHR) and airway inflammation have been established, has not been defined. We investigated the effects of blocking BLT1 on early- and late-phase development of AHR and airway inflammation in previously sensitized and challenged mice. Female BALB/c mice were sensitized (Days 1 and 14) and challenged (primary, Days 28-30) with ovalbumin. On Day 72, mice were challenged (secon... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5297001 Sat, 01 Oct 2011 04:00:00 +0100 5297001 http://www.medworm.com/index.php?rid=5297000&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21441380%26dopt%3DAbstract Authors: Dodmane PR, Schulte NA, Heires AJ, Band H, Romberger DJ, Toews ML Abstract A subset of workers in swine confinement facilities develops chronic respiratory disease. An aqueous extract of dust from these facilities (hogbarn dust extract [HDE]) induces IL-6 and IL-8 release and several other responses in isolated airway epithelial cells. The cell membrane receptors by which HDE initiates these responses have not been identified. Because several other inhaled agents induce airway epithelial cell responses through epidermal growth factor receptor (EGFR) activation, we hypothesized that HDE would activate EGFRs and that EGFRs would be required for some of the responses to HDE. Exposure of Beas-2B cells to HDE caused EGFR phosphorylation and downstream ERK activation, and both r... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5297000 Sat, 01 Oct 2011 04:00:00 +0100 5297000 http://www.medworm.com/index.php?rid=5296999&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21441383%26dopt%3DAbstract Authors: Fischer AJ, Lennemann NJ, Krishnamurthy S, Pócza P, Durairaj L, Launspach JL, Rhein BA, Wohlford-Lenane C, Lorentzen D, Bánfi B, McCray PB Abstract Recent reports postulate that the dual oxidase (DUOX) proteins function as part of a multicomponent oxidative pathway used by the respiratory mucosa to kill bacteria. The other components include epithelial ion transporters, which mediate the secretion of the oxidizable anion thiocyanate (SCN(-)) into airway surface liquid, and lactoperoxidase (LPO), which catalyzes the H(2)O(2)-dependent oxidation of the pseudohalide SCN(-) to yield the antimicrobial molecule hypothiocyanite (OSCN(-)). We hypothesized that this oxidative host defense system is also active against respiratory viruses. We evaluated the activity of oxidized LPO... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5296999 Sat, 01 Oct 2011 04:00:00 +0100 5296999 http://www.medworm.com/index.php?rid=5296998&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21474432%26dopt%3DAbstract This article summarizes these approaches and gives a critical overview about further candidate molecules that have been recently discussed as targets for an eosinophil-specific asthma therapy. PMID: 21474432 [PubMed - in process] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5296998 Sat, 01 Oct 2011 04:00:00 +0100 5296998 http://www.medworm.com/index.php?rid=5296997&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21474433%26dopt%3DAbstract Authors: Hibino Y, Morise M, Ito Y, Mizutani T, Matsuno T, Ito S, Hashimoto N, Sato M, Kondo M, Imaizumi K, Hasegawa Y Abstract To investigate the effects of capsaicinoids on airway anion transporters, we recorded and analyzed transepithelial currents in human airway epithelial Calu-3 cells. Application of capsaicin (100 μM) attenuated vectorial anion transport, estimated as short-circuit currents (I(SC)), before and after stimulation by forskolin (10 μM) with concomitant reduction of cytosolic cyclic AMP (cAMP) levels. The capsaicin-induced inhibition of I(SC) was also observed in the response to 8-bromo-cAMP (1 mM, a cell-permeable cAMP analog) and 3-isobutyl-1-methylxanthine (1 mM, an inhibitor of phosphodiesterases). The capsaicin-induced inhibition of I(SC) was attributed to... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5296997 Sat, 01 Oct 2011 04:00:00 +0100 5296997 http://www.medworm.com/index.php?rid=5229974&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21921238%26dopt%3DAbstract Authors: Chamoto K, Gibney BC, Lee GS, Lin M, Collings-Simpson D, Voswinckel R, Konerding MA, Tsuda A, Mentzer SJ Abstract In many species, pneumonectomy triggers compensatory lung growth that results in not only an increase in lung volume, but also an increase in alveolar number. Whether the associated alveolar angiogenesis involves the contribution of blood-borne progenitor cells is unknown. To identify and characterize blood-borne progenitor cells contributing to post-pneumonectomy lung growth in mice, we studied wild-type and wild-type/GFP parabiotic mice after left pneumonectomy. Within 21 days of pneumonectomy, there was a 3.2-fold increase in the number of lung endothelial cells. This increase in total endothelial cells was temporally associated with a 7.3-fold increase in t... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5229974 Thu, 15 Sep 2011 04:00:00 +0100 5229974 http://www.medworm.com/index.php?rid=5229973&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21921239%26dopt%3DAbstract Authors: Huang Y, Buscop-van Kempen M, Boerema-de Munck A, Swagemakers S, Driegen S, Mahavadi P, Meijer D, van Ijcken W, van der Spek P, Grosveld F, Günther A, Tibboel D, Rottier RJ Abstract Alveolarization of the developing lung is an important step towards the switch from intra-uterine life to oxygen rich air breathing after birth. The distal airways structurally change to minimize the gas exchange path and type II pneumocytes increase the production of surfactants, which are required to reduce the surface tension at the air-liquid interphase in the alveolus. Hypoxia Inducible Factor 2α (Hif2α) is an oxygen-regulated transcription factor expressed in endothelial and type II cells, and its expression increases towards the end of gestation. We investigated the role of Hif2α in ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5229973 Thu, 15 Sep 2011 04:00:00 +0100 5229973 http://www.medworm.com/index.php?rid=5229972&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21921240%26dopt%3DAbstract This study investigates PGE2 modulation of VEGF release by human lung fibroblasts. Human lung fibroblasts were cultured until 90% confluence in tissue culture plates, after which culture media were changed to serum-free DMEM with or without PGE2 and specific agonists and/or antagonists for each EP receptor. After 2 days, culture media were assayed for VEGF by ELISA. The results demonstrate that PGE2 and the EP2 agonist ONO-AE1-259-01 significantly stimulated VEGF release in a concentration-dependent manner. Agonists for other EP receptors did not stimulate VEGF release. The stimulatory effect of PGE2 was blocked by the EP2 antagonist AH6809 but was not blocked by the antagonists for other EP receptors. The protein kinase-A (PKA) inhibitor KT-5720 also blocked the stimulatory effect of PGE2... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5229972 Thu, 15 Sep 2011 04:00:00 +0100 5229972 http://www.medworm.com/index.php?rid=5218916&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21903873%26dopt%3DAbstract Authors: Ionescu LI, Alphonse RS, Arizmendi N, Morgan B, Abel M, Eaton F, Duszyk M, Vliagoftis H, Aprahamian TR, Walsh K, Thebaud B Abstract Asthma affects an estimated 300 million people worldwide and accounts for 1/250 deaths and 15 million disability-adjusted life years lost annually. Plastic-adherent bone marrow-derived cells (BMCs) administration holds therapeutic promise in regenerative medicine. However, given the low cell engraftment in target organs, including the lung, cell replacement cannot solely account for the reported therapeutic benefits. This suggests that BMCs may act by secreting soluble factors. BMCs also possess anti-inflammatory and immunomodulatory properties and may therefore be beneficial for asthma. Our objective was to investigate the therapeutic potenti... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5218916 Thu, 08 Sep 2011 04:00:00 +0100 5218916 http://www.medworm.com/index.php?rid=5218919&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21885676%26dopt%3DAbstract Conclusion: This study describes the key events during the development of S. pneumoniae empyema using a novel murine model of pneumonia-associated empyema that closely mimics human disease. This model will allow future assessment of the molecular mechanisms involved in the development of empyema and evaluation of potential new therapies. The data suggest that the pleural space is a protected space for the bacteria and that inhibiting transmigration of bacteria through mesothelial cells could prevent empyema. PMID: 21885676 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5218919 Thu, 01 Sep 2011 04:00:00 +0100 5218919 http://www.medworm.com/index.php?rid=5218918&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21885677%26dopt%3DAbstract In this study, we characterized the role of LRP-1 in uPAR processing, collagen synthesis, proteolysis and migration in pleural mesothelial cells (PMCs). When PMCs were treated with the pro-inflammatory cytokines TNF-α and IL-1β, LRP-1 significantly decreased at both the mRNA and protein levels (70% and 90% respectively, p<0.05). Consequently, uPA-mediated uPAR internalization was reduced by 80% in the presence of TNF-α or IL-1β (p<0.05). In parallel studies, LRP-1 neutralization with receptor associated protein; RAP, significantly reduced uPA-dependent uPAR internalization and increased uPAR stability in PMCs. LRP-1 deficient cells demonstrated increased uPAR t1/2 versus LRP-1 expressing PMCs. uPA enzymatic activity was also increased in LRP-1 deficient and neutralized cells and ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5218918 Thu, 01 Sep 2011 04:00:00 +0100 5218918 http://www.medworm.com/index.php?rid=5218917&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21885678%26dopt%3DAbstract Authors: Akuthota P, Melo RC, Spencer LA, Weller PF Abstract Eosinophils function in murine allergic airways inflammation as professional antigen-presenting cells (APCs). In murine professional APC cell types, optimal functioning of MHC Class II depends on its lateral association in plasma membranes and co-localization with the tetraspanin CD9 into detergent-resistant membrane microdomains (DRMs). With human eosinophils, we evaluated the localization of MHC Class II (HLA-DR) to DRMs and the functional significance of such localization. In GM-CSF-stimulated human eosinophils, antibody cross-linked HLA-DR co-localized by immunofluorescence microscopy focally on plasma membranes with both CD9 and the DRM marker ganglioside GM1. In addition, HLA-DR co-immunoprecipitates with CD9 after ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5218917 Thu, 01 Sep 2011 04:00:00 +0100 5218917 http://www.medworm.com/index.php?rid=5218915&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21908266%26dopt%3DAbstract Authors: Furuhashi K, Suda T, Hasegawa H, Suzuki Y, Hashimoto D, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Shibata K, Nakamura H, Chida K Abstract Mouse lung dendritic cells (LDCs) have been recently shown to contain two major sub-populations: CD103(+) CD11b(low or negative) (CD103(+) LDCs) and CD103(-) CD11b(high) LDCs (CD11b(high) LDCs). Although several studies demonstrated functional differences between these LDCs, it is not fully determined whether the two subpopulations induce distinct T helper (Th) cell responses. The present study was conducted to examine whether CD103(+) and CD11b(high) LDCs preferentially generate different Th responses. Naïve DO11.10 CD4(+) T cells were primed with CD103(+) or CD11b(high) LDCs obtained from normal BALB/c mouse. The primed T cells were ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5218915 Thu, 25 Aug 2011 04:00:00 +0100 5218915 http://www.medworm.com/index.php?rid=5175697&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21868710%26dopt%3DAbstract Authors: Williams L, Tucker TA, Koenig K, Allen T, Rao LV, Pendurthi U, Idell S Abstract Malignant pleural mesothelioma (MPM) is a rare cancer that is refractory to current treatments. It is characterized by robust transitional fibrin deposition that is in part promoted by tumor cells. MPM cells express tissue factor (TF) and its inhibitor; tissue factor pathway inhibitor (TFPI), but their contribution to the pathogenesis of MPM has been unclear. We found that REN MPM cells fail to express TFPI. Based on the tumor growth promoting properties of TF, we hypothesized that stable transfection of TFPI into REN MPM cells would decrease their aggressiveness. We tested our hypothesis using in vitro, in vivo and ex vivo analyses. TFPI knock-in decreased proliferation, invasion and TF activi... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5175697 Wed, 24 Aug 2011 23:00:00 +0100 5175697 http://www.medworm.com/index.php?rid=5175696&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21868711%26dopt%3DAbstract In this study, we sought to determine whether the anti-inflammatory effect of MUC1 is operative during nontypeable Haemophilus influenzae (NTHi) infection and, if so, which TLR pathway was affected. Our results showed that: (1) a lysate of NTHi increased early interleukin (IL)-8 release and later MUC1 protein production by A549 cells in dose- and time-dependent manners, compared with vehicle control; (2) both effects were attenuated following transfection of the cells with a TLR2-targeting small interfering (si) RNA, compared with a control siRNA; (3) NTHi-induced IL-8 release was suppressed by overexpression of MUC1 and enhanced by knockdown of MUC1; (4) TNF-α released following NTHi treatment was sufficient to upregulate MUC1, which was completely inhibited by pretreatment with a solubl... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5175696 Wed, 24 Aug 2011 23:00:00 +0100 5175696 http://www.medworm.com/index.php?rid=5175695&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21868712%26dopt%3DAbstract Authors: Skelly JR, Edge D, Shortt CM, Jones JF, Bradford A, O'Halloran KD Abstract Respiratory muscle dysfunction is implicated in the pathophysiology of obstructive sleep apnea syndrome (OSAS) - an oxidative stress disorder prevalent in males. Pharmacotherapy for OSAS is an attractive option and antioxidant treatments may prove beneficial in this regard. We sought to examine the effects of chronic intermittent hypoxia (CIH) on breathing and pharyngeal dilator muscle structure and function in male and female rats. Additionally, we tested the efficacy of antioxidant treatment in preventing (chronic administration) or reversing (acute administration) CIH-induced effects in male rats. Adult male and female Wistar rats were exposed to alternating cycles of normoxia and hypoxia (90s ea... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5175695 Wed, 24 Aug 2011 23:00:00 +0100 5175695 http://www.medworm.com/index.php?rid=5175694&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21868713%26dopt%3DAbstract This study has assessed the role of epidermal growth factor receptor (EGFR) signaling in mediating the effects of vesicant exposure on cytokine secretion and mucin production in human airway epithelial cells. Accordingly, normal human bronchial epithelial cells (NHBEC) in air-liquid interface were challenged apically with either 200 µM HN2 or medium alone (mock treatment, MT) and cultures were evaluated for receptor fate, IL-6 secretion and both total mucin and MUC5AC production. HN2 exposure induced both EGFR and (44/42)MAPK activation as well as ubiquitination and colocalization of the EGFR within lysosomal structures. Moreover, HN2 challenge induced subsequent up-regulation of IL-6 and MUC5AC at the mRNA and protein levels and also stimulated total mucin secretion in NHBEC. HN2-related... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5175694 Wed, 24 Aug 2011 23:00:00 +0100 5175694 http://www.medworm.com/index.php?rid=5101559&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21816964%26dopt%3DAbstract We report that wild-type Ras is S-nitrosylated and activated by nitrosative stress; and that it is denitrosylated by GSNO reductase. In human lung cancer, GSNO reductase activity and expression are decreased. Further, distribution of the enzyme - including its colocalization with wild-type Ras - is abnormal. We conclude that decreased GSNO reductase activity could leave the human lung vulnerable to the oncogenic effects of nitrosative stress, as is the case in the liver. This potential should be considered when developing therapies that inhibit pulmonary GSNO reductase to treat asthma and other conditions. PMID: 21816964 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5101559 Wed, 03 Aug 2011 23:00:00 +0100 5101559 http://www.medworm.com/index.php?rid=5101558&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21816965%26dopt%3DAbstract GENETIC DISRUPTION OF FRA-1 DECREASES SUSCEPTIBILITY TO ENDOTOXIN-INDUCED ACUTE LUNG INJURY AND MORTALITY IN MICE. Am J Respir Cell Mol Biol. 2011 Aug 4; Authors: Vaz M, Reddy NM, Subbiah R, Reddy SP The AP-1 transcription factor comprised of Jun and Fos family proteins distinctly regulate various cellular processes, including those involved in inflammation. Fra-1, a member of the Fos family, dimerizes with members of the Jun family and regulates gene expression in a context-dependent manner. Although respiratory toxicants are known to stimulate Fra-1 expression in the lung, whether Fra-1 promotes or decreases susceptibility to the development and progression of toxicant-induced lung diseases in vivo is not well established. To determine the role of Fra-1 in LPS-induced acute l... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5101558 Wed, 03 Aug 2011 23:00:00 +0100 5101558 http://www.medworm.com/index.php?rid=5053642&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21757681%26dopt%3DAbstract Authors: Clark CA, Thomas LK, Azghani AO Pseudomonas aeruginosa pulmonary infection compromises the human airway epithelium and can be especially devastating to immunocompromised or debilitated individuals. We have reported earlier that P. aeruginosa elastase (PE) increases paracellular permeability in epithelial cell monolayers by mechanisms involving tight junction (TJ) disruption and cytoskeletal reorganization, leading to destruction of epithelial barrier function. The aim of this study was to investigate putative TJ targets and potential mechanisms by which PE induces barrier disruption. We found that PE decreased localization of tight junction proteins occludin and ZO-1 in membrane fractions, as well as induced reorganization of F-actin within 1 hour. Although inhibition of PKC Î... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5053642 Wed, 20 Jul 2011 23:00:00 +0100 5053642 http://www.medworm.com/index.php?rid=5053641&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21778411%26dopt%3DAbstract Authors: Hristova M, Spiess PC, Kasahara DI, Randall MJ, Deng B, van der Vliet A The respiratory innate immune system is often compromised by tobacco smoke exposure, and previous studies indicated that acrolein, a reactive electrophile in tobacco smoke, may contribute to the immunosuppressive effects of smoking. Exposure of mice to acrolein at concentrations similar to those in cigarette smoke (5 ppm, 4 hrs) significantly suppressed alveolar macrophage responses to bacterial LPS, indicated by reduced induction of NOS2, TNF-α and IL-12p40. Mechanistic studies with bone marrow-derived macrophages or MH-S macrophages demonstrated that acrolein (1-30 µM) attenuated these LPS-mediated innate responses in association with depletion of cellular GSH, although GSH depletion itself was not ful... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5053641 Wed, 20 Jul 2011 23:00:00 +0100 5053641 http://www.medworm.com/index.php?rid=5053640&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21778412%26dopt%3DAbstract Authors: Parker D, Cohen TS, Alhede M, Harfenist BS, Martin FJ, Prince A The clinical manifestations of infection in cystic fibrosis are restricted to the lung and involve a limited number of pathogens, suggesting a specific defect in mucosal immunity. We postulated that CTFR mutations could affect the activation of type I Interferon signaling in airway epithelial cells, which function in immune surveillance and initiate the recruitment and activation of immune cells. In response to Pseudomonas aeruginosa infection Ifnb was induced by over 100 fold in the murine lung and STAT1 phosphorylation was similarly induced by the expected TLR4/TRIF/MD2/TBK1 cascade. P. aeruginosa stimulation of CF (IB3) cells and control (C-38) human cell lines similarly resulted in IFN-β induction, but signif... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5053640 Wed, 20 Jul 2011 23:00:00 +0100 5053640 http://www.medworm.com/index.php?rid=5053639&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21778413%26dopt%3DAbstract Authors: Yeager ME, Belchenko DD, Nguyen CM, Colvin KL, Ivy DD, Stenmark KR Endothelin-1 is a potent vasoactive peptide that is present in chronically high levels in humans with pulmonary hypertension and in animal models of the disease. Recently, the unfolded protein response has been implicated in a variety of diseases, including pulmonary hypertension. In addition, there is increasing evidence for pathological, persistent inflammation in the pathobiology of this disease. We sought to investigate whether endothelin-1 might engage the unfolded protein response and thus link inflammation and the production of hyaluronic acid by pulmonary artery smooth muscle cells. Using immunoblot, real-time PCR, immunofluorescence, and luciferase assays, we found that endothelin-1 induces both a tran... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5053639 Wed, 20 Jul 2011 23:00:00 +0100 5053639 http://www.medworm.com/index.php?rid=5053638&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21778414%26dopt%3DAbstract Conclusion: ECM produced from COPD fibroblasts following CSE exposure has pro-proliferative effects. Thus the ECM in patients with COPD may create an environment which promotes airway remodeling. PMID: 21778414 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5053638 Wed, 20 Jul 2011 23:00:00 +0100 5053638 http://www.medworm.com/index.php?rid=5053644&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21757679%26dopt%3DAbstract Authors: Zhou X, Wu W, Hu H, Milosevic J, Konishi K, Kaminski N, Wenzel SE Primary human distal lung/parenchymal fibroblasts (DLF) exhibit a different phenotype from airway fibroblasts (AF), including expression of high levels of α-smooth muscle actin (α-SMA). The scope of the differences between these anatomically differentiated fibroblasts or the mechanisms driving them are unknown. To determine whether different regional fibroblast characteristics are predicted by distinct genomic differences in AF vs DLF, matched human fibroblast pairs isolated from proximal and distal lung were evaluated. Microarray analysis was performed on 12 matched fibroblast pairs (4 normal and 8 asthmatics) and validated by quantitative real-time PCR (qRT-PCR). Potential functional implications of these di... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5053644 Wed, 13 Jul 2011 23:00:00 +0100 5053644 http://www.medworm.com/index.php?rid=5053643&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21757680%26dopt%3DAbstract Authors: Fuchimoto Y, Kanehiro A, Miyahara N, Koga H, Ikeda G, Waseda K, Tanimoto Y, Ueha S, Kataoka M, Gelfand EW, Tanimoto M Chemokine receptor 5 (CCR5) is expressed on dendritic cells, macrophages, CD8 cells, memory CD4 T cells, and stromal cells and is frequently used as a marker of Th1 cells. Interventions that abrogate CCR5 or interfere with its ligand binding have been shown to alter Th2-induced inflammatory responses. The role of CCR5 on allergic airway responses is not defined. CCR5-deficient (CCR5-/-) and wild-type (CCR5+/+) mice were sensitized and challenged with ovalbumin (OVA) and allergic airway responses were monitored 48 hrs after the last OVA challenge. Cytokine levels in lung cell culture supernatants were also assessed. CCR5-/- mice showed significantly lower airway... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5053643 Wed, 13 Jul 2011 23:00:00 +0100 5053643 http://www.medworm.com/index.php?rid=5053645&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21749980%26dopt%3DAbstract This study examined the role of Notch in the epithelial-mesenchymal transition (EMT) and myofibroblast differentiation of cultured RLE-6TN cells (i.e., rat alveolar epithelial cells). The activation of Notch, either by ectopic expression of the Notch intracellular domain or by the co-culture of RLE-6TN cells with L-Jagged1 cells, induces the expression of smooth muscle α-actin (SMA) and other mesenchymal marker genes (collagen I and vimentin), and reduces the expression of epithelial marker genes (E-cadherin, occludin, and zonula occludens-1). The pharmacologic inhibition of the endogenous Notch signal significantly inhibited the transforming growth factor-β (TGF-β)-induced expression of SMA. Cell migratory capacity was increased by Notch. Luciferase assays revealed that the CC(A/T)(6)G... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5053645 Thu, 30 Jun 2011 23:00:00 +0100 5053645 http://www.medworm.com/index.php?rid=5006726&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21719794%26dopt%3DAbstract In conclusion, stimulation of GABAB receptors on human airway smooth muscle cells rapidly mobilizes intracellular Ca (2+) stores by inositol phosphate synthesis through the activation of PLC-β that is stimulated by Gβγ protein liberated from Gi proteins coupled to GABAB receptors. Furthermore, crosstalk between GABA B receptors and Gq-coupled receptors potentiates inositol phosphate synthesis, transient [Ca(2+)]i increases and smooth muscle contraction through Gi proteins. PMID: 21719794 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5006726 Wed, 29 Jun 2011 23:00:00 +0100 5006726 http://www.medworm.com/index.php?rid=5006725&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21719795%26dopt%3DAbstract Authors: Drake JI, Bogaard HJ, Mizuno S, Clifton B, Xie B, Gao Y, Dumur CI, Fawcett P, Voelkel NF, Natarajan R Right heart failure is the cause of death of most patients with severe pulmonary arterial hypertensive (PAH) disorders, yet little is known about the cellular and molecular causes of right ventricular failure (RVF). We first showed a differential gene expression pattern between normal rat right and left ventricles and postulated that there exists a molecular right heart failure program which distinguishes RVF from adaptive RV hypertrophy (RVH) and may also differ in some aspects from a left heart failure program. We used two models of adaptive RVH to characterize, using microarrays and transcriptional sequencing strategies, by a gene expression pattern reflective of growth and... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=5006725 Wed, 29 Jun 2011 23:00:00 +0100 5006725 http://www.medworm.com/index.php?rid=4960818&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21685153%26dopt%3DAbstract Conclusions: Our studies indicate that DIO2 is a novel ALI candidate gene whose non-synonymous Thr92Ala coding variant (rs225014) confers ALI protection. Increased DIO2 expression may dampen the ALI inflammatory response thereby strengthening the premise that thyroid hormone metabolism is intimately linked to the integrated response to inflammatory injury in critically ill patients. PMID: 21685153 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4960818 Thu, 16 Jun 2011 23:00:00 +0100 4960818 http://www.medworm.com/index.php?rid=4960817&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21685154%26dopt%3DAbstract Authors: Reynolds PR, Stogsdill JA, Stogsdill MP, Heimann NB Receptors for advanced glycation end-products (RAGE) are cell-surface receptors expressed by pulmonary tissue that influence alveolar type (AT)II - ATI transition required for normal alveolar formation. However, the precise contribution of RAGE in interactions between pulmonary epithelium and splanchnic mesenchyme during lung organogenesis remains uncertain. In order to test the hypothesis that RAGE misexpression adversely affects lung morphogenesis, conditional transgenic mice were generated that over-express RAGE. Mice that over-express RAGE throughout embryogenesis experienced 100% mortality and significant lung hypoplasia coincident with large, vacuous areas in the periphery when compared to normal airway and alveolar arc... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4960817 Thu, 16 Jun 2011 23:00:00 +0100 4960817 http://www.medworm.com/index.php?rid=4960816&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21685155%26dopt%3DAbstract Authors: Churg A, Sin DD, Wright JL There are a very large number of experimental approaches that prevent cigarette smoke-induced emphysema in laboratory animals, but the few similar treatments that have been tried in humans have had minimal effects, leading to questions of whether animal models of COPD are of any use in developing treatments for human disease. We review possible reasons for this problem: (1) humans usually get treated when they have severe (GOLD III/IV) COPD, but animal models only produce mild (GOLD I/II) disease that never progresses after smoking cessation and never develops spontaneous exacerbations; ie, animal models are not models of severe human disease and probably can't be used to model treatment of severe disease; (2) Animal models have concentrated on emphy... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4960816 Thu, 16 Jun 2011 23:00:00 +0100 4960816 http://www.medworm.com/index.php?rid=4960826&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21659655%26dopt%3DAbstract Authors: Reddy NM, Potteti HR, Mariani TJ, Biswal S, Reddy SP Oxidant stress, resulting from an excess of reactive electrophiles produced in the lung by both resident (epithelial and endothelial) and infiltrated leukocytes, is thought to play an obligatory role in tissue injury and abnormal repair. Previously, using a conventional (whole-body) knockout model, we have shown that antioxidative gene induction regulated by the transcription factor Nrf2 is critical for mitigating oxidant-induced (hyperoxic) stress as well as for preventing and resolving tissue injury and inflammation in vivo. However, the contribution to pathogenic acute lung injury (ALI) of the cellular stress produced by the resident versus infiltrated leukocytes is still largely undefined in vivo. To address this critica... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4960826 Wed, 08 Jun 2011 23:00:00 +0100 4960826 http://www.medworm.com/index.php?rid=4960825&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21659656%26dopt%3DAbstract This study tests the hypotheses that ERM proteins are phosphorylated in response to 2ME, and this phosphorylation is involved in 2ME-induced barrier dysfunction. We show that 2ME application leads to a dramatic increase in ERM phosphorylation level; this increase is attenuated in cells pretreated with microtubule stabilizer taxol. In human pulmonary artery endothelial cells (HPAEC), ERM phosphorylation occurs in p38- and PKC-dependent manner; p38 activation appears to be upstream from PKC activation in response to 2ME. Phosphorylated ERM are localized at the cell periphery during the early phase of response to 2ME (15 min), and co-localize with F-actin branching points during the later phase of response (60 min). Using siRNA approach, we next show that individual ERM depletion significantl... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4960825 Wed, 08 Jun 2011 23:00:00 +0100 4960825 http://www.medworm.com/index.php?rid=4960824&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21659657%26dopt%3DAbstract In conclusion, markers previously associated at or near GWS with spirometric measures were tested for association with COPD status in data from 4 COPD case-control studies, and three loci showed evidence of association with COPD susceptibility at a 5% false discovery rate. PMID: 21659657 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4960824 Wed, 08 Jun 2011 23:00:00 +0100 4960824 http://www.medworm.com/index.php?rid=4960823&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21659658%26dopt%3DAbstract Authors: Sharma V, Singh BP, Arora N Allergens with reduced IgE binding and intact T cell reactivity are required for safety and efficacy of immunotherapy (IT). Curvularia lunata is an important fungus for respiratory allergic disorders having cross-reactive and specific allergens. Previously, we have identified major allergens namely Cur l 1 (31 kDa, serine protease), Cur l 2 (48 kDa, enolase) and Cur l 3 (12 kDa, cytochrome c) from this fungus. Further, Cur l 3 epitope-peptide P6 showed immunogenicity and higher IgE binding, where cysteine and histidine were observed vital for IgE binding. Thus, this peptide and three derivatives with reduced IgE binding were selected for analysis in mice. In the present study, effect of IT was assessed with Cur l 3, P6, its derivatives (P6.1 to 6.3)... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4960823 Wed, 08 Jun 2011 23:00:00 +0100 4960823 http://www.medworm.com/index.php?rid=4960822&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21659659%26dopt%3DAbstract Authors: Alapati D, Rong M, Chen S, Hehre D, Rodriguez MM, Lipson KE, Wu S Despite recent advances in neonatal intensive care and surfactant therapy, bronchopulmonary dysplasia (BPD) continues to be one of the most common long-term pulmonary complications associated with preterm birth. Clinical efforts to prevent and treat BPD have been largely unsuccessful due to its multifactorial nature and poorly understood disease process. Connective tissue growth factor (CTGF) is a matricellular protein that plays an important role in tissue development and remodeling. Previous studies have demonstrated that hyperoxia exposure upregulates CTGF expression in neonatal rat lungs. Whether CTGF overexpression plays a role in the pathogenesis of BPD and whether CTGF antagonism has a therapeutic potenti... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4960822 Wed, 08 Jun 2011 23:00:00 +0100 4960822 http://www.medworm.com/index.php?rid=4960821&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21659660%26dopt%3DAbstract Authors: Dechecchi MC, Nicolis E, Mazzi P, Cioffi F, Bezzerri V, Lampronti I, Huang S, Wiszniewski L, Gambari R, Scupoli MT, Berton G, Cabrini G Investigation on novel targets for the treatment of Cystic Fibrosis (CF) lung inflammation is a major priority, considering that no effective therapy is available for this purpose. Consistently with the evidence that the sphingolipid (SL) ceramide regulates airway inflammation and infection in CF mice and patients, SLs have been identified as targets to treat pulmonary disorders, including CF. Because miglustat, an inhibitor of the synthesis of glycosphingolipids, reduces the P.aeruginosa-dependent transcription of IL-8 gene in bronchial cells, we examined the effect of miglustat and amitriptyline, another drug affecting ceramide metabolism, o... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4960821 Wed, 08 Jun 2011 23:00:00 +0100 4960821 http://www.medworm.com/index.php?rid=4960820&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21659661%26dopt%3DAbstract Authors: Shlyonsky V, Ben Soussia I, Naeije R, Mies F Alteration in the control of Bone Morphogenetic Protein -regulated genes and increased expression of endothelin-1 are both believed to play important roles in the still incompletely understood pathobiology of pulmonary vascular remodeling and fibrosis. Recent studies have drawn attention to the contribution of adventitial fibroblast activation in these phenomena. Since chloride channels are involved in the control of physiological function of fibroblasts, we hypothesized that these channels are differentially regulated by BMP's and endothelin. We measured chloride ion currents by whole-cell path-clamping in cultured primary human pulmonary fibroblasts. The application of BMP-2 prevented activation of these currents by hypotonic chal... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4960820 Wed, 08 Jun 2011 23:00:00 +0100 4960820 http://www.medworm.com/index.php?rid=4960819&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21659662%26dopt%3DAbstract Authors: Brownell I, Ramírez-Valle F, Sanchez M, Prystowsky S Despite its recognition as a distinct granulomatous disease for over a century, the etiology of sarcoidosis remains to be defined. Since the early 1900s, infectious agents have been suspected in causing sarcoidosis. For much of this time, mycobacteria were considered a likely culprit, yet until recently, the supporting evidence has been tenuous at best. In this review, we evaluate the reported association between mycobacteria and sarcoidosis. Historically, mycobactrial infection has been investigated using histologic stains, cultures of lesional tissue or blood, and identification of bacterial nucleic acids or bacterial antigens. More recently advances in biochemical, molecular, and immunological methods have produced a mor... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4960819 Wed, 08 Jun 2011 23:00:00 +0100 4960819 http://www.medworm.com/index.php?rid=4960829&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21653905%26dopt%3DAbstract Authors: Holtzman M, Patel D, Kim H, You Y, Zhang Y PMID: 21653905 [PubMed - in process] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4960829 Tue, 31 May 2011 23:00:00 +0100 4960829 http://www.medworm.com/index.php?rid=4960828&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21653906%26dopt%3DAbstract Authors: Kreisel D, Lai J, Richardson SB, Ibricevic A, Nava RG, Lin X, Li W, Kornfeld CG, Miller MJ, Brody SL, Gelman AE, Krupnick AS Activated T lymphocytes are abundant in the airway during lung allograft rejection. Based on respiratory viral studies, it is the current paradigm that T cells cannot divide in the airway, and that their accumulation in the lumen of the respiratory tract is the exclusive result of recruitment from other sites, such as mediastinal lymph nodes. Here, we show that CD8(+) T cell activation and proliferation can occur in the airway after orthotopic lung transplantation. We also demonstrate that airway epithelium expresses major histocompatibility class I predominantly on the apical surface, both in vitro and in vivo, and initiates CD8(+) T cell responses in a... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4960828 Tue, 31 May 2011 23:00:00 +0100 4960828 http://www.medworm.com/index.php?rid=4960827&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21653907%26dopt%3DAbstract This study indicates that mucin production is prominent in developing murine lungs and that Muc5b is an early, abundant, and persistent marker of bronchial airway secretory cells, thereby implicating it as an intrinsic component of homeostatic mucosal defense in the lungs. PMID: 21653907 [PubMed - in process] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4960827 Tue, 31 May 2011 23:00:00 +0100 4960827 http://www.medworm.com/index.php?rid=4807114&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531958%26dopt%3DAbstract Authors: Matute-Bello G, Downey G, Moore BB, Groshong SD, Matthay MA, S.sky AS, Kuebler WM, Acute lung injury (ALI) is well defined in humans, but there is no agreement as to the main features of acute lung injury in animal models. A Committee was organized to determine the main features that characterize ALI in animal models and to identify the most relevant methods to assess these features. We used a Delphi approach in which a series of questionnaires were distributed to a panel of experts in experimental lung injury. The Committee concluded that the main features of experimental ALI include histological evidence of tissue injury, alteration of the alveolar capillary barrier, presence of an inflammatory response, and evidence of physiological dysfunction; they recommended that, to d... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4807114 Sat, 30 Apr 2011 23:00:00 +0100 4807114 http://www.medworm.com/index.php?rid=4807115&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21527775%26dopt%3DAbstract Authors: Hubbard LL, Wilke CA, White ES, Moore BB Hematopoietic stem cell transplant (HSCT) patients are susceptible to infection despite hematopoietic reconstitution. In a murine model of syngeneic bone marrow transplantation (BMT), we previously reported that BMT mice have impaired host defense against Pseudomonas aeruginosa pneumonia, due to lung overproduction of prostaglandin E2 (PGE2). Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an effector in the PGE2 signaling pathway that negatively regulates AM phagocytosis and bacterial killing. Therefore, we wanted to determine whether overproduction of PGE2 post-BMT inhibits AM host defense by upregulating PTEN phosphatase activity. We found that PTEN activity is elevated in BMT AMs in response to increased PGE2 signa... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4807115 Wed, 27 Apr 2011 23:00:00 +0100 4807115 http://www.medworm.com/index.php?rid=4702142&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21454805%26dopt%3DAbstract In this study, we show nuclear β-catenin accumulation in lung fibroblasts from patients with systemic sclerosis-associated advanced pulmonary fibrosis. Forced activation of β-catenin signaling in normal human lung fibroblasts promotes their proliferation, migration, and invasion through type 1 collagen in vitro but is not sufficient to activate classic markers of fibroblast activation (e.g., TGF-β, α-smooth muscle actin, CTGF), although Wnt/β-catenin signaling may contribute to their expression. These findings indicate that activation of β-catenin signaling in pulmonary fibroblasts may be a common feature of lung fibrosis, contributing to fibrogenic activities associated with the disease. PMID: 21454805 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4702142 Wed, 06 Apr 2011 23:00:00 +0100 4702142 http://www.medworm.com/index.php?rid=4702141&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21474432%26dopt%3DAbstract This article aims at summarizing these approaches and gives a critical overview about further candidate molecules that are recently discussed as targets for an eosinophil specific asthma therapy. PMID: 21474432 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4702141 Wed, 06 Apr 2011 23:00:00 +0100 4702141 http://www.medworm.com/index.php?rid=4643274&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21398620%26dopt%3DAbstract Authors: Huizar I, Malur A, Midgette YA, Kukoly C, Chen P, Ke PC, Podila R, Rao AM, Wingard CJ, Dobbs L, Barna BP, Kavuru MS, Thomassen MJ Abstract Lung granulomas are associated with numerous conditions including: inflammatory disorders, environmental pollutant exposure, and infection. Osteopontin is a chemotactic cytokine produced by macrophages and implicated in extracellular matrix remodeling. Furthermore, osteopontin is upregulated in granulomatous disease and osteopontin null mice have reduced granuloma formation. Animal models currently used to investigate chronic lung granulomatous inflammation have a pathological resemblance, but lack the chronic nature observed in human granulomatous disease. Carbon nanoparticles are generated as byproducts of combustion. Interestingly, exper... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4643274 Fri, 18 Mar 2011 00:00:00 +0100 4643274 http://www.medworm.com/index.php?rid=4643273&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21421907%26dopt%3DAbstract Authors: Moore TV, Clay BS, Cannon JL, Histed A, Shilling RA, Sperling AI Our lab and others have reported that ICOS-/- mice have a defect in Th2-mediated airway inflammation, which has been attributed to reduced Th2 differentiation in the absence of ICOS signaling. Interestingly, the number of CD4 T cells present in the airways and lungs after sensitization and challenge is significantly reduced in ICOS-/- mice. We now show that this reduction is not simply attributable to reduced proliferation of ICOS-/- cells, as significantly more ICOS-/- than wild-type activated CD4 T cells are present in the lymph nodes, suggesting that ICOS-/- CD4 T cells migrated into the lymph nodes more than wild-type CD4 T cells. Further investigation revealed that activated ICOS-/- CD4 T cells express highe... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4643273 Fri, 18 Mar 2011 00:00:00 +0100 4643273 http://www.medworm.com/index.php?rid=4643272&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21421908%26dopt%3DAbstract Conclusions: These data identify the importance of the LTB4-BLT1 pathway in the development of late phase allergen-induced airway responsiveness following secondary airway challenge, in mice with established airway disease. PMID: 21421908 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4643272 Fri, 18 Mar 2011 00:00:00 +0100 4643272 http://www.medworm.com/index.php?rid=4643271&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21421909%26dopt%3DAbstract Authors: Sun S, Wang H, Zhao G, An Y, Guo Y, Du L, Song H, Qiao F, Yu H, Wu X, Atkinson C, Jiang S, Tomlinson S, Zhou Y The widely used herbicide paraquat (PQ) is highly toxic to humans and claims thousands of lives from both accidental and voluntary ingestion. Nowadays no effective treatment has been applied clinically. The pathological mechanisms of PQ poisoning and resulting acute lung injury (ALI) are not well understood. We developed and characterized a mouse model of PQ-induced ALI and studied the role of complement in the pathogenesis of PQ poisoning. Intraperitoneal administration of PQ caused dose and time-dependent lung damage and mortality, with an associated inflammatory response. Within 24 hours of PQ-induced ALI, there was significantly increased expression of the complem... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4643271 Fri, 18 Mar 2011 00:00:00 +0100 4643271 http://www.medworm.com/index.php?rid=4472882&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21297077%26dopt%3DAbstract Conclusions: Selective inhibition of soluble TNF suppresses inflammation, hyperreactivity, and remodeling in transgenic and wild-type mouse models of allergic airway disease, and suggests possible safety advantages for therapies that preserve the immunoprotective functions of transmembrane TNF. PMID: 21297077 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4472882 Fri, 04 Feb 2011 00:00:00 +0100 4472882 http://www.medworm.com/index.php?rid=4472881&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21297078%26dopt%3DAbstract Authors: Chang EH, Pezzulo AA, Zabner J Cell junction proteins connect epithelial cells to each other and to the basement membrane. Genetic mutations of these proteins can cause alterations in some epithelia leading to varied phenotypes such as deafness, renal disease, skin disorders, and cancer. This review examines if genetic mutations in these proteins affect the function of lung airway epithelia. We review cell junction proteins with examples of disease mutation phenotypes in humans and in mouse knockout models. We also review which of these genes are expressed in airway epithelium by microarray expression profiling and immunocytochemistry. Last, we present a comprehensive literature review to find the lung phenotype when cell junction and adhesion genes are mutated or subject to t... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4472881 Fri, 04 Feb 2011 00:00:00 +0100 4472881 http://www.medworm.com/index.php?rid=4472880&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21297079%26dopt%3DAbstract Conclusions: IL-6 is the main causative agent of IL-6 cytokine family-induced emphysema and operates to induce apoptosis in the lung. We propose that discrete targeting of IL-6 signaling may provide an effective therapeutic strategy against human lung disease. PMID: 21297079 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4472880 Fri, 04 Feb 2011 00:00:00 +0100 4472880 http://www.medworm.com/index.php?rid=4472879&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21297080%26dopt%3DAbstract Authors: Perry MM, Hui CK, Whiteman M, Wood ME, Adcock I, Kirkham P, Michaeloudes C, Chung KF Hydrogen sulfide (H2S) is synthesised intracellularly by the enzymes cystathione-γ-lyase (CSE) and cystathionine-β-synthase (CBS), and is proposed to be a gasotransmitter with effects in modulating inflammation and cellular proliferation. We determined a role of H2S in airway smooth muscle (ASM) function. ASM were removed from resection or transplant donor lungs and were placed in culture. Proliferation of ASM was induced by fetal calf serum (FCS) and the pro-inflammatory cytokine interleukin (IL)-1β. Proliferation of ASM and IL-8 release were measured by BrdU incorporation and ELISA, respectively. Exposure of ASM to H2S donors inhibited this proliferation and IL-8 release. Methemoglobin, a... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4472879 Fri, 04 Feb 2011 00:00:00 +0100 4472879 http://www.medworm.com/index.php?rid=4472878&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21297081%26dopt%3DAbstract Authors: Pino-Yanes M, Ma SF, Sun X, Tejera P, Corrales A, Blanco J, Pérez-Méndez L, Espinosa E, Muriel A, Blanch L, Garcia JG, Villar J, Flores C Sepsis is the most common cause of acute lung injury (ALI), leading to organ dysfunction and death in critically ill patients. Previous studies have associated variants of interleukin-1 receptor-associated kinase genes (IRAKs) with differential immune response to pathogens and with outcomes during sepsis, and revealed that increased IRAK3 gene expression levels were correlated with poor outcomes during sepsis. Here we explored whether common variants of the IRAK3 gene were associated with susceptibility and outcomes of severe sepsis. After polymorphism discovery, we genotyped a subset of seven single nucleotide polymorphisms (SNPs) in 336 ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4472878 Fri, 04 Feb 2011 00:00:00 +0100 4472878 http://www.medworm.com/index.php?rid=4406287&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21257922%26dopt%3DAbstract Authors: Masuno K, Haldar SM, Jeyaraj D, Mailloux C, Huang X, Panettieri Jr RA, Jain MK, Gerber AN Glucocorticoids (GCs), which activate glucocorticoid receptor (GR) signaling and thus modulate gene expression, are widely used to treat asthma. Glucocorticoids exert their therapeutic effects in part through modulating airway smooth muscle (ASM) structure and function. However, the effects of genes that are regulated by GCs on airway function are not fully understood. We therefore used transcription profiling to study the effects of a potent GC, dexamethasone, on human ASM gene expression at 4 and 24 hours. After 24 hours of dexamethasone treatment, nearly 7500 genes had statistically distinguishable changes in expression; qPCR validation of a 40-gene subset of putative GR-regulated gene... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4406287 Fri, 21 Jan 2011 00:00:00 +0100 4406287 http://www.medworm.com/index.php?rid=4406286&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21257923%26dopt%3DAbstract Authors: Segawa S, Goto D, Yoshiga Y, Horikoshi M, Sugihara M, Hayashi T, Chino Y, Matsumoto I, Ito S, Sumida T Interstitial lung disease (ILD) is induced by various factors in humans. However, the exact mechanism of ILD remains elusive. The aim of this study was to determine the role of NK1.1(+) γδT cells in ILD. Injection of interleukin (IL)-18 plus IL-2 (IL-18/IL-2) into C57BL6 (B6) mice induced acute ILD that resembled early-stage human ILD. Accumulation of NK1.1(+) γδT cells similar to NK cells was noted in the lungs. The TCR Vγ and Vδ repertoires of NK1.1(+) γδT cells indicated polyclonal expansion. The expression of IL-2 receptor β (Rβ) and IL-18Rβ on NK1.1(+) γδT cells was higher than on NK1.1(-) γδT cells. IL-18/IL-2 stimulated proliferation of NK1.1(+) γδT ce... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4406286 Fri, 21 Jan 2011 00:00:00 +0100 4406286 http://www.medworm.com/index.php?rid=4406285&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21257924%26dopt%3DAbstract Conclusions. Such a mechanism could at least partly explain the effects exerted by crocidolite fibers in mesothelial cells. PMID: 21257924 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4406285 Fri, 21 Jan 2011 00:00:00 +0100 4406285 http://www.medworm.com/index.php?rid=4406284&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21257925%26dopt%3DAbstract Authors: Bir N, Lafargue M, Howard M, Goolaerts A, Roux J, Carles M, Cohen MJ, Iles KE, Fernández JA, Griffin JH, Pittet JF Inhibition of the small GTPase RhoA attenuates the development of pulmonary edema and restores a positive alveolar fluid clearance in a mouse model of P. aeruginosa pneumonia. Activated protein C (aPC) blocks development of an unfavorably low small GTPase Rac1/RhoA activity ratio in lung endothelium through EPCR/PAR-1-dependent signaling mechanisms that include transactivating the sphingosine-1-phosphate (S1P) pathway. However, it is it not known if aPC's cytoprotective effects can attenuate the development of pulmonary edema and death associated with P. aeruginosa pneumonia in mice. Thus, we determined whether normalization of a depressed ratio of activated Rac1... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4406284 Fri, 21 Jan 2011 00:00:00 +0100 4406284 http://www.medworm.com/index.php?rid=4406283&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21257926%26dopt%3DAbstract In this report we demonstrate that LMW HA causes a rapid, significant and sustained down regulation of the A2aR. CD44 was found to be necessary for LMW HA to down modulate the A2aR as was protein kinase c signaling. We also demonstrate that LMW HA induces A2aR downregulation during inflammation in vivo and that this downregulation can be blocked by treatment with an HA blocking peptide. Since adenosine plays a critical role in limiting inflammation, our data provide a novel mechanism whereby LMW HA itself may further augment inflammation. By defining the pro- and anti-inflammatory properties of extracellular matrix components, we will be better able to identify specific pharmacologic targets as potential therapies. PMID: 21257926 [PubMed - as supplied by publisher] (Source: American Jo... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4406283 Fri, 21 Jan 2011 00:00:00 +0100 4406283 http://www.medworm.com/index.php?rid=4406282&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21257927%26dopt%3DAbstract Authors: Farnand AW, Eastman AJ, Herrero R, Hanson JF, Mongovin S, Altemeier WA, Matute-Bello G Activation of the Fas/FasL system is associated with activation of apoptotic and pro-inflammatory pathways that lead to the development of acute lung injury. Previous studies in chimeric mice and macrophage-depleted mice suggested that the main effector cell in Fas-mediated lung injury is not a myeloid cell but likely an epithelial cell. The goal of this study was to determine whether epithelial cells release pro-inflammatory cytokines following Fas activation and to identify the relevant pathways. Incubation of the murine alveolar epithelial cell line MLE-12 with the Fas-activating mAb Jo2 resulted in release of the CXC chemokine KC in a dose-dependent manner. KC release was not prevented b... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4406282 Fri, 21 Jan 2011 00:00:00 +0100 4406282 http://www.medworm.com/index.php?rid=4406294&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21239602%26dopt%3DAbstract Authors: Harvey PR, Tarran R, Garoff S, Myerburg MM In the cystic fibrosis (CF) lung the airway surface liquid (ASL) volume is depleted, impairing mucus clearance from the lung and leading to chronic airway infection and obstruction. Several therapeutics have been developed that aim to restore normal airway surface hydration to the CF airway, yet preclinical evaluation of these agents is hindered by the paucity of methods available to directly measure the ASL. Therefore, we sought to develop a straightforward approach to measure the ASL volume that would serve as the basis for a standardized method to assess mucosal hydration using readily available resources. Primary human bronchial epithelial (HBE) cells cultured at an air-liquid interface (ALI) develop a liquid meniscus at the edge ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4406294 Fri, 14 Jan 2011 00:00:00 +0100 4406294 http://www.medworm.com/index.php?rid=4406293&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21239603%26dopt%3DAbstract Conclusion: These findings for the first time reveal in an in vitro model of acute inflammation that the immunomodulatory effects are not limited to volatile anesthetics, but are associated with a much broader class of CF3 group-containing molecules. The immunomodulatory effects could now be provided in a hydrophilic, injectable formulation for the future treatment of patients suffering from acute organ injury such as acute lung injury in environments not suitable for volatile anesthetics. PMID: 21239603 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4406293 Fri, 14 Jan 2011 00:00:00 +0100 4406293 http://www.medworm.com/index.php?rid=4406292&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21239604%26dopt%3DAbstract Authors: Simon GC, Martin RJ, Smith S, Thaikoottathil J, Bowler RP, Barenkamp SJ, Chu HW Airway bacterial infections continue to be a major problem in lung diseases including asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. Increased Th2 cytokines such as IL-13 are observed in lung diseases, and may contribute to bacterial infections. However, how Th2 cytokines affect bacterial infection remains unknown. MUC18, an adhesion molecule previously shown to be involved in the pathogenesis of malignant melanoma, has been recently identified in airway epithelial cells of COPD patients. Our major goals are to investigate MUC18 regulation by IL-13, and the role of MUC18 in bacterial adherence to epithelial cells. Human airway tissues, brushed bronchial epithelial cells f... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4406292 Fri, 14 Jan 2011 00:00:00 +0100 4406292 http://www.medworm.com/index.php?rid=4406291&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21239605%26dopt%3DAbstract Authors: Kelly C, Shields MD, Elborn JS, Schock BC Persistent activation of NF-κB is central to the pathogenesis of many inflammatory lung disorders including Cystic Fibrosis, Asthma and Chronic Obstructive Pulmonary Disease. A20 is an endogenous negative regulator of NF-κB signalling which has been widely described in autoimmune and inflammatory disorders including Diabetes and Crohn's disease, but which has received little attention in terms of chronic lung disorders. This review examines the existing body of research on A20 regulation of NF-κB signalling and details the mechanism and regulation of A20 action focusing, where possible, on pulmonary inflammation. A20 and its associated signalling molecules are highlighted as being of potential therapeutic interest for the treatment ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4406291 Fri, 14 Jan 2011 00:00:00 +0100 4406291 http://www.medworm.com/index.php?rid=4406290&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21239606%26dopt%3DAbstract Conclusion: Exposure to early postnatal hyperoxia contributed additively to CS-induced COPD changes in adult mice. These results may be relevant to a growing population of preterm children who sustained lung injury in the newborn period and may be exposed to cigarette smoke in later life. PMID: 21239606 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4406290 Fri, 14 Jan 2011 00:00:00 +0100 4406290 http://www.medworm.com/index.php?rid=4406289&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21239607%26dopt%3DAbstract Authors: Kikuchi N, Ishii Y, Morishima Y, Yageta Y, Haraguchi N, Yamadori T, Masuko H, Sakamoto T, Yanagawa T, Warabi E, Ishii T, Hizawa N Oxidative stress plays an important role in the pathogenesis of acute lung injury and pulmonary fibrosis. Peroxiredoxin I is a cellular antioxidant enzyme induced under stress conditions. In the present study, the protective effects of peroxiredoxin I on the development of bleomycin-induced acute pulmonary inflammation and pulmonary fibrosis were investigated using peroxiredoxin I-deficient mice. Survival of peroxiredoxin I-deficient mice after bleomycin administration was significantly lower than that of wild-type mice, corresponding with enhanced acute pulmonary inflammation and fibrosis. The level of inflammatory cytokines and chemokines, such as... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4406289 Fri, 14 Jan 2011 00:00:00 +0100 4406289 http://www.medworm.com/index.php?rid=4406288&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21239608%26dopt%3DAbstract This study provides insight into the influenza-induced innate immunity in differentiated human ATII cells and demonstrates that the alveolar epithelium is a critical part of the initial innate immune response to influenza. Keywords: human type II cell; influenza; chemokine; PI3k; differentiation; SP-A; SP-D. PMID: 21239608 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4406288 Fri, 14 Jan 2011 00:00:00 +0100 4406288 http://www.medworm.com/index.php?rid=4340126&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21216970%26dopt%3DAbstract Conclusions: Nrf2 regulates NTHI-induced airway inflammation characterized by lymphocytic and plasma cell infiltration and the activation of lung dendritic cells and B cell responses in mice. Nrf2 may be a potential therapeutic target in limiting bacterial infection-induced airway inflammation that drives COPD exacerbations. PMID: 21216970 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4340126 Fri, 07 Jan 2011 00:00:00 +0100 4340126 http://www.medworm.com/index.php?rid=4340125&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21216971%26dopt%3DAbstract In this study, we have extended our findings to show that functional impairment of these effector cells is not initiated by bone marrow derived cells and is independent of proliferation in the lung tissue. Of critical importance, we have also determined that the susceptibility to functional inactivation is a common property shared by most effector cells. Finally, we show that the susceptibility to loss of function is actively regulated throughout differentiation. While naïve cells, like effector cells, are negatively regulated as a result of residence in the lung, memory cells exhibit profound resistance to functional inactivation. The selective resistance of memory cells may allow the host to limit damage during the effector phase while retaining a protective response that can effectivel... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4340125 Fri, 07 Jan 2011 00:00:00 +0100 4340125 http://www.medworm.com/index.php?rid=4340124&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21216972%26dopt%3DAbstract Authors: Pittet LA, Quinton LJ, Yamamoto K, Robson BE, Ferrari JD, Algul H, Schmid RM, Mizgerd JP NF-κB regulates cytokine expression to initiate and control the innate immune response to lung infections. The NF-κB protein RelA is critical for pulmonary host defense during Streptococcus pneumoniae pneumonia, but cell-specific roles of this transcription factor remain to be determined. We hypothesized that RelA in alveolar macrophages contributes to cytokine expression and host defense during pneumococcal pneumonia. To test this hypothesis, we compared mice lacking RelA exclusively in myeloid cells (RelAΔ/Δ) to littermate controls (RelAF/F). Alveolar macrophages from RelAΔ/Δ mice expressed no full-length RelA, demonstrating effective targeting. Alveolar macrophages from RelAΔ/Δ ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4340124 Fri, 07 Jan 2011 00:00:00 +0100 4340124 http://www.medworm.com/index.php?rid=4340123&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21216973%26dopt%3DAbstract Authors: Nakamura T, Matsushima M, Hayashi Y, Shibasaki M, Imaizumi K, Hashimoto N, Shimokata K, Hasegawa Y, Kawabe T Quercetin is one of the flavonoids with a wide variety of cytoprotective and modulatory functions. Heme oxygenase 1 (HO-1) is an inducible enzyme, or its reaction product, carbon monoxide (CO), which confers cellular protection for a number of conditions and diseases associated with oxidative or inflammatory lung injury. Furthermore, quercetin has been reported to be a potent HO-1 inducer in several cell types. We hypothesized that quercetin suppresses collagen production in fibroblasts by the induction of HO-1. In the present study, we showed that quercetin suppressed the TGF-ß-induced collagen production in NIH3T3 cells and in normal human lung fibroblasts. This supp... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4340123 Fri, 07 Jan 2011 00:00:00 +0100 4340123 http://www.medworm.com/index.php?rid=4340122&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21216974%26dopt%3DAbstract Authors: Hirota JA, Ask K, Farkas L, Smith JA, Ellis R, Rodriguez-Lecompte JC, Kolb M, Inman MD Airway smooth muscle (ASM) hyperplasia in asthma likely contributes considerably to functional changes and investigating the mechanisms behind proliferation of these cells may lead to therapeutic benefit. PDGF-BB is a well known ASM mitogen in vitro, but has yet to be directly explored using in vivo mouse models in the context of ASM proliferation and airway physiology. We set out to determine the in vivo influence of PDGF-BB on gene transcripts encoding contractile proteins, ASM proliferation, and airway responsiveness, using an adenovirus overexpression system and a model of chronic allergen exposure. We used adenovirus technology to selectively overexpress PDGF-BB in the airway epithelium... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4340122 Fri, 07 Jan 2011 00:00:00 +0100 4340122 http://www.medworm.com/index.php?rid=4340121&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21216975%26dopt%3DAbstract Conclusions: IFNγ and its downstream targets may significantly contribute to the final common pathway of hyperoxia-induced injury in the developing lung and human BPD. PMID: 21216975 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4340121 Fri, 07 Jan 2011 00:00:00 +0100 4340121 http://www.medworm.com/index.php?rid=4277996&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21169554%26dopt%3DAbstract Conclusions: In a mouse model of emphysema, progressive decline in lung function is sensitive to the development of airspace heterogeneity governed by local mechanical. PMID: 21169554 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4277996 Fri, 17 Dec 2010 00:00:00 +0100 4277996 http://www.medworm.com/index.php?rid=4277995&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21169555%26dopt%3DAbstract Authors: Zhong Q, Zhou B, Ann DK, Minoo P, Liu Y, Banfalvi A, Krishnaveni MS, Dubourd M, Demaio L, Willis BC, Kim KJ, Dubois RM, Crandall ED, Beers MF, Borok Z Endoplasmic reticulum (ER) stress has been implicated in alveolar epithelial type II (AT2) cell apoptosis in idiopathic pulmonary fibrosis. We hypothesized that ER stress (either chemically induced or due to accumulation of misfolded proteins) is also associated with epithelial-mesenchymal transition (EMT) in alveolar epithelial cells (AEC). ER stress inducers thapsigargin (TG) or tunicamycin (TN) increased expression of ER chaperone Grp78 and spliced X-box binding protein (XBP)-1, decreased epithelial markers E-cadherin and zonula occludens-1 (ZO-1), increased the myofibroblast marker α-smooth muscle actin (α-SMA), and induce... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4277995 Fri, 17 Dec 2010 00:00:00 +0100 4277995 http://www.medworm.com/index.php?rid=4277994&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21169556%26dopt%3DAbstract Conclusions: IL-6 contributes to the cardiovascular dysfunction related to LPS and pre-treatment with budesonide/formoterol reduces systemic expression of IL-6 and improves cardiovascular dysfunction. ICS/LABA may reduce acute cardiovascular events related to ALI. PMID: 21169556 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4277994 Fri, 17 Dec 2010 00:00:00 +0100 4277994 http://www.medworm.com/index.php?rid=4186575&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21075861%26dopt%3DAbstract This study uses a rat model to examine a possible mechanism of O3-induced neural hyper-responsiveness during a critical developmental period, postnatal day (PD)-6 that may be mediated by the neurotrophin Nerve Growth Factor (NGF) and result in enhanced release of the inflammatory neuropeptide substance P (SP) from airway nerves. Rat pups between PD6-PD28 were euthanized 24hr after exposure to O3 (2ppm, 3hrs) or filtered air (FA), to establish a timeline of NGF synthesis or exposed to O3 or NGF on PD6 or PD21 and re-exposed to O3 on PD28 and euthanized on PD29. Measurement endpoints were NGF mRNA in tracheal epithelial cells, NGF protein in bronchoalveolar lavage, airway SP-nerve fiber density (NFD) and SP-positive airway neurons in vagal ganglia. Acute O3 exposure increased NGF in bronchoa... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4186575 Fri, 12 Nov 2010 00:00:00 +0100 4186575 http://www.medworm.com/index.php?rid=4186574&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21075862%26dopt%3DAbstract Authors: Weng M, Raher MJ, Leyton P, Combs TP, Scherer PE, Bloch KD, Medoff BD Remodeling of the pulmonary arteries is a common feature in the heterogeneous group of disorders that cause pulmonary hypertension. In these disorders, the remodeled pulmonary arteries often demonstrate inflammation and accumulation of pulmonary artery smooth muscle cells (PASMC) within the vessels. Adipose tissue secretes multiple bioactive mediators (adipokines) which can influence both inflammation and remodeling, suggesting that adipokines could contribute to the development of pulmonary hypertension. We recently reported that in a model of pulmonary hypertension induced by vascular inflammation, deficiency of the adipokine adiponectin (APN) was associated with extensive PASMC proliferation and increased... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4186574 Fri, 12 Nov 2010 00:00:00 +0100 4186574 http://www.medworm.com/index.php?rid=4186573&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21075863%26dopt%3DAbstract In conclusion, we have cloned and elucidated the entire MUC19 gene, which will facilitate understanding of the function and regulation of this important, yet understudied, mucin gene in airway diseases. PMID: 21075863 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4186573 Fri, 12 Nov 2010 00:00:00 +0100 4186573 http://www.medworm.com/index.php?rid=4167608&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21057104%26dopt%3DAbstract This report summarizes currently available therapeutic options and also translates experimental research to discuss potential novel biomarkers and therapeutic strategies derived from new concepts in pathogenesis. PMID: 21057104 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4167608 Fri, 05 Nov 2010 00:00:00 +0100 4167608 http://www.medworm.com/index.php?rid=4167607&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21057105%26dopt%3DAbstract Authors: Zaidi S, Gallos G, Yim PD, Xu D, Sonett JR, Panettieri Jr RA, Gerthoffer W, Emala CW γ-amino butyric acid (GABA) is a primary inhibitory neurotransmitter in the central nervous system and is classically released by fusion of synaptic vesicles with the plasma membrane or by egress via GABA transporters. Recently a GABAergic system comprised of GABAA and GABAB receptors has been identified on airway epithelial and smooth muscle cells that regulate mucus secretion and contractile tone of airway smooth muscle. Additionally, the enzyme that synthesizes GABA (glutamic acid decarboxylase (GAD) has been identified in airway epithelial cells; however, the mechanism(s) by which this synthesized GABA is released from epithelial intracellular stores is unknown. We questioned whether any ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4167607 Fri, 05 Nov 2010 00:00:00 +0100 4167607 http://www.medworm.com/index.php?rid=4167606&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21057106%26dopt%3DAbstract Authors: Morin C, Fortin S, Cantin AM, Rousseau E The effects of CRBM-0244, a newly synthesized DHA derivative, were determined on lung inflammation and airway hyperresponsiveness in an in vitro model of TNFα-stimulated human bronchi as well as in an in vivo model of allergic asthma. Mechanical tension measurements revealed that CRBM-0244 prevented bronchial hyperresponsiveness in TNFα-pretreated human bronchi. Moreover, CRBM-0244 treatments resulted in a decrease in NFκB activation and COX2 over-expression triggered by TNFα. Inhibition of PPARγ with GW9662 abolished CRBM-0244 mediated anti-inflammatory effects. CRBM-0244 reduced Ca2+ sensitivity of bronchial smooth muscle through a decrease in CPI-17 phosphorylation and expression level. Results also revealed an over-expression o... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4167606 Fri, 05 Nov 2010 00:00:00 +0100 4167606 http://www.medworm.com/index.php?rid=4108044&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20971885%26dopt%3DAbstract Authors: Zhang Y, Hinojosa ME, Yoo N, Holtzman MJ PMID: 20971885 [PubMed - in process] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4108044 Thu, 28 Oct 2010 08:35:07 +0100 4108044 http://www.medworm.com/index.php?rid=4108049&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20971879%26dopt%3DAbstract Authors: Nawijn MC, Piavaux BJ, Jeurink PV, Gras R, Reinders MA, Stearns T, Foote S, Hylkema MN, Groot PC, Korstanje R, van Oosterhout AJ Allergic asthma is a complex disease characterized by airway hyperreactivity (AHR), Th2 driven eosinophilic airway inflammation, high allergen-specific IgE (anti-OVA IgE) levels in serum and airway remodeling. Since asthma susceptibility has a strong genetic component, we aimed to identify new asthma susceptibility genes in the mouse by analyzing the asthma phenotypes of the Leishmania major resistant (lmr) recombinant congenic (RC) strains. The lmr RC strains are derived from C57BL/6 and BALB/c intercrosses and carry congenic loci on chromosome 17 (lmr1) and 9 (lmr2) in both backgrounds. Whereas the lmr2 locus on chromosome 9 only contributes to a s... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4108049 Thu, 21 Oct 2010 23:00:00 +0100 4108049 http://www.medworm.com/index.php?rid=4108048&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20971880%26dopt%3DAbstract Conclusion Our data show that cigarette smoke accelerates polymerization of Z-AT by oxidative modification, which in so doing further reduces pulmonary defense and increases neutrophil influx into the lungs. These novel findings provide a molecular explanation for the striking observation of premature emphysema in ZZ homozygotes who smoke, and raise the prospect of anti-oxidant therapy in Z-AT related COPD. PMID: 20971880 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4108048 Thu, 21 Oct 2010 23:00:00 +0100 4108048 http://www.medworm.com/index.php?rid=4108047&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20971881%26dopt%3DAbstract Authors: Cushing L, Kuang PP, Qian J, Shao F, Wu J, Little F, Thannickal VJ, Cardoso WV, Lu J miRNAs are small regulatory RNAs that control gene expression by translational suppression and destabilization of target mRNAs. There is increasing evidence that miRNAs regulate genes associated with fibrosis in organs, such as the heart, kidney, liver and the lung. In a large scale screening for miRNAs potentially involved in bleomycin-induced fibrosis, we found expression of miR-29 family members significantly reduced in fibrotic lungs. Analysis of normal lungs showed the presence of miR-29 in subsets of interstitial cells of the alveolar wall, pleura and at the entrance of the alveolar duct, known sites of pulmonary fibrosis. miR-29 levels inversely correlated with the expression levels of ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4108047 Thu, 21 Oct 2010 23:00:00 +0100 4108047 http://www.medworm.com/index.php?rid=4108046&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20971882%26dopt%3DAbstract Authors: Lee YC, Oslund KL, Thai P, Velichko S, Fujisawa T, Duong T, Denison MS, Wu R 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental toxicant. Epidemiological studies have associated TCDD exposure with the development of chronic obstructive pulmonary disease, which is manifested by mucous/goblet cell hyperplasia (GCH). The purpose of this research was to elucidate the pathway/mechanisms that lead to TCDD-induced gene expression in both primary normal human bronchial epithelial (NHBE) cells and an immortalized cell line, HBE1 under air-liquid interface conditions. TCDD exposure induced a time-dependent elevation of MUC5AC mRNA and protein synthesis, and cytochrome p450 1A1 (CYP1A1) expression in these cells. Treatment with an aryl hydrocarbon receptor (AhR) antagon... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4108046 Thu, 21 Oct 2010 23:00:00 +0100 4108046 http://www.medworm.com/index.php?rid=4108045&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20971883%26dopt%3DAbstract Authors: Rezaee F, Gibson LF, Piktel D, Othumpangat S, Piedimonte G Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children. The pathophysiology of this infection in the respiratory system has been studied extensively, but little is known about its consequences in other systems. We studied whether RSV infects human bone marrow stromal cells (BMSC) in vitro and in vivo, and investigated whether and how this infection affects BMSC structure and hematopoietic support function. Primary human BMSC were infected in vitro with recombinant RSV expressing green fluorescent protein. Also, RNA from naïve BMSC was amplified by polymerase chain reaction, and the products were sequenced to confirm homology with the RSV genome. The BMSC cytoskeleton wa... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4108045 Thu, 21 Oct 2010 23:00:00 +0100 4108045 http://www.medworm.com/index.php?rid=4063936&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20935189%26dopt%3DAbstract Conclusions: Peripheral airway smooth muscle mass is stable in chronically affected animals subjected to antigenic exposure. This increased mass is maintained in a dynamic equilibrium by an elevated cellular turnover, suggesting that targeting smooth muscle proliferation could be effective at decreasing chronic remodeling. PMID: 20935189 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4063936 Thu, 07 Oct 2010 23:00:00 +0100 4063936 http://www.medworm.com/index.php?rid=4063935&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20935190%26dopt%3DAbstract In this study, we sought to identify inhibitory mechanisms that impair alveolar macrophage function. Balb/c mice acutely exposed to four cigarettes over 4Hrs prior to intranasal lipopolysaccharide (1μg, LPS) treatment displayed significantly reduced airway neutrophilia and TNFα expression. Balb/c derived MH-S alveolar macrophage cells exposed to cigarette smoke extract (CSE) displayed a similar inhibitory response to LPS stimulation. Induction of inflammatory genes by rTNFα (100ng/mL) was also impaired by CSE. Since both pathways converge on NFκB, analysis of IκBα degradation and p65 phosphorylation was assessed and shown to be blunted by CSE. CSE also blocked AP-1 activity by inhibiting p38 MAPK in a reduced glutathione (GSH) reversible manner. Induction of specific TLR negative reg... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4063935 Thu, 07 Oct 2010 23:00:00 +0100 4063935 http://www.medworm.com/index.php?rid=4063934&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20935191%26dopt%3DAbstract In this study, we investigated the contribution of goblet cells to airway epithelial ATP release. Primary human bronchial epithelial (HBE) cultures, typically dominated by ciliated cells, were induced to develop goblet cell metaplasia by infection with respiratory syncytial virus (RSV) or treatment with interleukin-13 (IL-13). Under resting conditions, goblet cell metaplastic cultures displayed enhanced mucin secretion, which was accompanied by increased rates of ATP release and mucosal surface adenosine accumulation as compared to non-metaplastic control HBE cultures. Intracellular calcium chelation [1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM)] or disruption of the secretory pathways (nocodazole, brefeldin A, and N-ethylmaleimide) decreased... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4063934 Thu, 07 Oct 2010 23:00:00 +0100 4063934 http://www.medworm.com/index.php?rid=4063933&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20935192%26dopt%3DAbstract Authors: Horvath KM, Brighton LE, Zhang W, Carson JL, Jaspers I Epidemiological evidence suggests that cigarette smoking is a risk factor for influenza infection, but the mechanisms underlying this susceptibility remain unknown. To ascertain if airway epithelial cells from smokers have a decreased ability to orchestrate an influenza-induced immune response, we established a model utilizing differentiated nasal epithelial cells (NEC) from nonsmokers and smokers co-cultured with peripheral blood monocyte-derived dendritic cells (mono-DCs) from nonsmokers. NEC/mono-DC co-cultures were infected with influenza A virus and analyzed for influenza-induced immune responses 24 h post infection. We observed that NEC from smokers, as well as mono-DCs co-cultured with NECs from smokers, have suppre... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4063933 Thu, 07 Oct 2010 23:00:00 +0100 4063933 http://www.medworm.com/index.php?rid=4063932&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20935193%26dopt%3DAbstract In this study, we have shown that the proinflammatory cytokines, IL-1ß and IL-17A, both of which utilize the NF-B pathway, are potent inducers of MUC5B mRNA expression in both well-differentiated primary normal human bronchial epithelial (NHBE) cells and the human bronchial epithelial cell line, HBE1. MUC5B induction by these cytokines was both time- and dose-dependent and was attenuated by the small molecule inhibitor, NF-B inhibitor III, as well as p65 small-interfering RNA, suggesting that the regulation of MUC5B expression by these cytokines is via an NF-B-based transcriptional mechanism. Deletion analysis with the MUC5B promoter construct demonstrated that IL-1ß- and IL-17A-induced promoter -reporter activities reside within the -4.17kb to -2.56kb region relative to the transcriptio... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4063932 Thu, 07 Oct 2010 23:00:00 +0100 4063932 http://www.medworm.com/index.php?rid=4004120&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20870892%26dopt%3DAbstract Conclusions: The selective interaction of CCL3 with its receptor, CCR1, is critical for radiation-induced lung inflammation and fibrosis, and these conditions can be largely prevented by a small molecule inhibitor of CCR1. PMID: 20870892 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4004120 Thu, 23 Sep 2010 23:00:00 +0100 4004120 http://www.medworm.com/index.php?rid=4004077&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20870893%26dopt%3DAbstract We report that increased membrane septin-2 localization mediates decreases in paracellular permeability by altering cortical actin arrangement in human airway epithelial cells. This phenomenon occurs in response to both physiologic levels of shear stress and a pathologic stimulus, particular matter exposure. The resulting changes in barrier function in response to septin-2 redistribution have a significant impact on the ability of the apical ligand, EGF to interact with its receptor, EGFR, which is segregated to the basolateral side in airway epithelial cells, suggesting that the dynamic regulation of the epithelial barrier function is essential in regulating signaling responses to extracellular stimuli. These findings indicate that septin-2 plays a fundamental role in regulating barrier f... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4004077 Thu, 23 Sep 2010 23:00:00 +0100 4004077 http://www.medworm.com/index.php?rid=4004025&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20870894%26dopt%3DAbstract Authors: Chustz RT, Nagarkar DR, Poposki JA, Favoreto Jr S, Avila PC, Schleimer RP, Kato A The IL-1 family of cytokines, which now includes 11 members, is well known to participate in inflammation. Although the most recently recognized IL-1 family cytokines (IL-1F5-11) have been shown to be expressed in airway epithelial cells, the regulation of their expression and function in the epithelium has not been extensively studied. We investigated the regulation of IL-1F5-11 in primary normal human bronchial epithelial cells. Messenger RNAs for IL-1F6 and IL-1F9, but not IL-1F5, IL-1F8 or IL-1F10, were significantly up-regulated by TNF, IL-1ß, IL-17 and the TLR3 ligand dsRNA. Messenger RNAs for IL-1F7 and IL-1F11 (IL-33) were weakly up-regulated by some of the cytokines tested. Notably, m... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4004025 Thu, 23 Sep 2010 23:00:00 +0100 4004025 http://www.medworm.com/index.php?rid=4003967&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20870895%26dopt%3DAbstract Authors: Dyugovskaya L, Polyakov A, Ginsberg D, Lavie P, Lavie L Apoptosis of polymorphonuclear cells (PMNs) is a fundamental mechanism to halt inflammation. It limits PMNs’ lifespan and thereby decreases tissue injury. In PMNs, unlike in other cells, hypoxia profoundly inhibits apoptosis. However, most studies investigating hypoxic effects on PMN functions focus on acute or chronic sustained hypoxia (SH). Thus, the mechanisms by which intermittent hypoxia (IH) affects PMN apoptosis are not known. Flow cytometry and western blotting were employed to evaluate mechanisms of constitutive and tumor necrosis factor (TNF)-α-mediated PMN apoptosis in IH. The levels of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), tumor necrosis factor receptor (TNFR)-2,... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4003967 Thu, 23 Sep 2010 23:00:00 +0100 4003967 http://www.medworm.com/index.php?rid=4003903&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20870896%26dopt%3DAbstract In conclusion, increased levels of ADMA can indirectly alter NO signaling through decreased cellular BH4 levels secondary to the disruption of Hsp90/GCH1 interactions and the CHIP dependent proteasomal degradation of GCH1. PMID: 20870896 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory Cell and Molecular Biology) American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4003903 Thu, 23 Sep 2010 23:00:00 +0100 4003903 http://www.medworm.com/index.php?rid=4003834&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20870897%26dopt%3DAbstract Authors: Zhu M, Flynt L, Ghosh S, Mellema M, Banerjee A, Williams E, Panettieri Jr RA, Shore SA Airway smooth muscle (ASM) cells have been reported to contribute to the inflammation of asthma. Because the thiazolidinediones (TZDs) have anti-inflammatory effects, we examined the effect of troglitazone and rosiglitazone on the release of inflammatory moieties from cultured human ASM cells. Troglitazone dose-dependently reduced IL-1β-induced IL-6 and VEGF release, TNFα-induced eotaxin and RANTES release, and IL-4 induced eotaxin release. Rosiglitazone also inhibited TNFα-stimulated RANTES release. Even though TZDs are known to activate peroxisome proliferator-activated receptor-gamma (PPARγ), these anti-inflammatory effects were not affected by a specific PPARγ inhibitor (G... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4003834 Thu, 23 Sep 2010 23:00:00 +0100 4003834 http://www.medworm.com/index.php?rid=4003601&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20870898%26dopt%3DAbstract This study examined the role of Notch in epithelial-mesenchymal transition (EMT) and myofibroblast differentiation of cultured RLE-6TN cells, rat alveolar epithelial cells. Activation of Notch, either by ectopic expression of Notch intracellular domain or by coculture of RLE-6TN cells with L-Jagged1 cells, induced the expression of the smooth muscle α-actin (SMA) and other mesenchymal marker genes (collagen I and vimentin) and reduced the expression of the epithelial marker genes (E-cadherin, occludin and zonula occludens-1). Pharmacological inhibition of endogenous Notch signal significantly inhibited transforming growth factor-β (TGF-β)-induced SMA expression. Cell migratory capacity was increased by Notch. Luciferase assays revealed that CArG box and TGF-β-control element (T... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4003601 Thu, 23 Sep 2010 23:00:00 +0100 4003601 http://www.medworm.com/index.php?rid=4004294&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20855648%26dopt%3DAbstract Authors: Song W, Wei S, Liu G, Yu Z, Estell K, Yadav AK, Schwiebert LM, Matalon S Exposure to chlorine (Cl2) damages airway and alveolar epithelia resulting in acute lung injury and reactive airway dysfunction syndrome (RADS). We evaluated the efficacy and mechanisms by which Arformoterol, a long term β2 agonist, administered post exposure, mitigated the extent of this injury. Exposure of C57BL/6 mice to 400 ppm Cl2 for 30 min increased respiratory system resistance and airway responsiveness to aerosolized methacholine (assessed by FlexiVent), up to six days post exposure and decreased Na(+)-dependent alveolar fluid clearance (AFC). iNOS (-/-) mice developed similar degrees of airway hyper-reactivity as wild type controls after Cl2 exposure indicating that reactive intermediates fro... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4004294 Sun, 19 Sep 2010 23:00:00 +0100 4004294 http://www.medworm.com/index.php?rid=4004264&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20855649%26dopt%3DAbstract Authors: Qiao J, Li A, Jin X, Wang J The pathogenesis of allergic asthma is characterized by airway inflammation, eosinophilia and airway hyper-responsiveness (AHR). In the present study, we investigated the anti-inflammatory effects of mastic, obtained from the stem and the leaves of Pistacia lentiscus trees, on allergic asthma. In an ovalbumin (OVA)-induced mouse asthma model, mastic significantly inhibited eosinophilia while reducing airway AHR and suppressing the production of inflammatory cytokines (IL-5 and IL-13) as well as chemokines (eotaxin, eotaxin2 and RANTES) in bronchoalveolar lavage fluid (BALF). Moreover, mastic potently inhibited eotaxin-induced eosinophil chemotaxis in vitro without influencing eotaxin receptor-chemokine receptor 3 (CCR3) expressions. These results su... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4004264 Sun, 19 Sep 2010 23:00:00 +0100 4004264 http://www.medworm.com/index.php?rid=4004234&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20855650%26dopt%3DAbstract Authors: Tompkins DH, Besnard V, Lange AW, Keiser AR, Wert SE, Bruno MD, Whitsett JA Sox2, a transcription factor critical for the maintenance of embryonic stem cells and induction of pluripotent stem cells, is also expressed exclusively in the conducting airway epithelium of the lung where it is required for differentiation of nonciliated, goblet, and ciliated cells. To determine the role of Sox2 in respiratory epithelial cells, Sox2 was selectively and conditionally expressed in nonciliated airway epithelial cells and alveolar type II cells in the adult mouse. Sox2 induced epithelial cell proliferation within 3 days of expression. Epithelial cell proliferation was associated with increased Ki-67 and cyclin D1 staining. Expression of cell cycle genes, including FoxM1, Ccna2 (Cyclin A2... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4004234 Sun, 19 Sep 2010 23:00:00 +0100 4004234 http://www.medworm.com/index.php?rid=4004199&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20855651%26dopt%3DAbstract Authors: Kreisel D, Lai J, Richardson SB, Ibricevic A, Nava RG, Lin X, Li W, Kornfeld CG, Miller MJ, Brody SL, Gelman AE, Krupnick AS Activated T lymphocytes are abundant in the airway during lung allograft rejection. Based on respiratory viral studies, it is the current paradigm that T cells cannot divide in the airway and that their accumulation in the lumen of the respiratory tract is the exclusive result of recruitment from other sites, such as mediastinal lymph nodes. Here we show that CD8(+) T cell activation and proliferation can occur in the airway after orthotopic lung transplantation. We also demonstrate that airway epithelium expresses MHC Class I predominantly on the apical surface, both in vitro and in vivo, and initiates CD8(+) T cell responses in a polarized fashion favo... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4004199 Sun, 19 Sep 2010 23:00:00 +0100 4004199 http://www.medworm.com/index.php?rid=4004162&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20855652%26dopt%3DAbstract Authors: Deschamps K, Cromlish W, Weicker S, Lamontagne S, Huszar SL, Gauthier JY, Mudgett JS, Guimond A, Romand R, Frossard N, Percival MD, Slipetz D, Tan CM Cathepsin S (Cat S) is predominantly expressed in antigen presenting cells and is upregulated in several preclinical models of antigen-induced inflammation, suggesting a role in the allergic response. Prophylactic dosing of an irreversible Cat S inhibitor has been shown to attenuate pulmonary eosinophilia in mice, supporting the hypothesis that Cat S inhibition prior to the initiation of airway inflammation is beneficial in airway disease. In addition, Cat S has been shown to play a role in more distal events in the allergic response. To determine where Cat S inhibition may impact on the allergic response, we employed complementa... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=4004162 Sun, 19 Sep 2010 23:00:00 +0100 4004162 http://www.medworm.com/index.php?rid=3938991&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20813992%26dopt%3DAbstract This study investigated whether MCP-1 is the mediator of the systemic inflammation of alveolar hypoxia. Experiments in rats and in alveolar macrophages and peritoneal mast cells showed: 1. Alveolar hypoxia (10% O2 breathing, 60 min) produced a rapid (5min) increase in plasma MCP-1 concentration of conscious intact rats, but not of alveolar macrophage-depleted rats. 2. Degranulation occurred when mast cells were immersed in the plasma of hypoxic intact rats, but not of alveolar-macrophage depleted rats. 3. MCP-1 added to normoxic rat plasma and supernatant of normoxic alveolar macrophages produced concentration-dependent degranulation of immersed mast cells. 3. MCP-1 applied to the mesentery of normoxic intact rats replicated the inflammation of alveolar hypoxia, and 4.The CCR2b receptor an... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=3938991 Wed, 01 Sep 2010 23:00:00 +0100 3938991 http://www.medworm.com/index.php?rid=3938990&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20813993%26dopt%3DAbstract Authors: Cuttica MJ, Langenickel T, Noguchi A, Machado RF, Gladwin MT, Boehm M Pulmonary hypertension is a vascular proliferative disease characterized by pulmonary artery remodeling due to dysregulated endothelial and smooth muscle cell proliferation. While the role inflammation plays in the development of the disease is not well defined, plexogenic lesions in human disease have been characterized by perivascular inflammation composed in part by T cells. We sought to explore the role of T cell infiltration on pulmonary vascular remodeling following endothelial cell damage. We induced endothelial cell damage using monocrotaline and isolated the role of T cells by utilizing Rag1tm1Mom mice and performing adoptive T cell transfer. We found that monocrotaline causes a pulmonary vascular e... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=3938990 Wed, 01 Sep 2010 23:00:00 +0100 3938990 http://www.medworm.com/index.php?rid=3915771&cid=s_36890_67_f&fid=36890&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20802087%26dopt%3DAbstract The objective of this study was to obtain a better understanding of the interactions between HIV-1 and cocaine in order to help uncover the mechanism(s) of HIV-PAHâs development. We observed that exposure of HIV-infected macrophages or HIV-Tat treated pulmonary endothelial cells to cocaine enhanced the expression of platelet-derived growth factor (PDGF)-BB, while simultaneous treatment with Tat and cocaine exacerbated both the disruption of tight junction proteins (TJPs) with enhanced permeability in pulmonary endothelial cells and the proliferation of pulmonary smooth muscle cells (pSMCs) compared to either treatment alone. Histological examination of HIV+IVDU human lung sections showed signs of early pulmonary arteriopathy, severe down-modulation of TJPs and increased expression of PD... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=3915771 Thu, 26 Aug 2010 23:00:00 +0100 3915771