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. Wed, 17 Mar 2010 16:33:43 +0100 http://www.medworm.com/index.php?rid=3372243&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%3D20228386%26dopt%3DAbstract Authors: Crystal RG PMID: 20228386 [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=3372243 Wed, 17 Mar 2010 15:06:05 +0100 3372243 http://www.medworm.com/index.php?rid=3362727&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%3D20224071%26dopt%3DAbstract Authors: Miller JD, Lankford SM, Adler KB, Brody AR Mesenchymal stem cells (MSCs) reside within tissues such as bone marrow, cord blood, and dental pulp and can differentiate into other mesenchymal cell types. Differentiated MSCs, called circulating fibrocytes, have been demonstrated in human lungs and migrate to injured lung tissue in experimental models. It is likely that MSCs migrate from the bone marrow to sites of injury by following increasing chemokine concentrations. In the present study, we show that primary mouse bone marrow mesenchymal stem cells (BM-MSC) exhibit directed chemotaxis through transwell inserts towards increasing concentrations of the chemokines C5a, SDF-1alpha, and MCP-1. Prior research has indicated that myristoylated alanine-rich C kinase substrate (MARCKS) ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=3362727 Thu, 11 Mar 2010 00:00:00 +0100 3362727 http://www.medworm.com/index.php?rid=3362726&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%3D20224072%26dopt%3DAbstract Authors: Eddleston J, Lee RU, Doerner AM, Herschbach J, Zuraw BL Exposure to cigarette smoke is associated with a significant increase in the risk for respiratory viral infections. The airway epithelium is the primary target for both cigarette smoke and respiratory viral infection. Here we investigated the effects of cigarette smoke on the response of airway epithelial cells to rhinovirus infection. We found that preexposure of BEAS-2B or primary NHBE cells to cigarette smoke extract (CSE) reduced the induction of CXCL10 and CCL5 mRNA by either poly I:C (a viral mimic) or human rhinovirus 16 (HRV-16) infection. HRV-16 induced CXCL10 and CCL5 release was also significantly suppressed by CSE. Activation of the IFN mediator STAT-1 as well as activation of JNK by poly I:C and HRV-16 were p... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=3362726 Thu, 11 Mar 2010 00:00:00 +0100 3362726 http://www.medworm.com/index.php?rid=3291408&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%3D20167933%26dopt%3DAbstract Authors: Scheckenbach KL, Losa D, Dudez T, Bacchetta M, O'Grady S, Crespin S, Chanson M Stimulation of the cystic fibrosis transmembrane conductance regulator (CFTR) by protease-activated receptors (PARs) at the basolateral membranes and adenosine receptors (ADO-Rs) at the apical membrane maintain airway surface liquid (ASL) volume, which is required to ensure hydrated and clearable mucus. Both pathways involved the release of prostaglandin E2 (PGE2) and stimulation of their basolateral receptors (EP-Rs). Our goal was to determine whether gap junctions contribute to the coordination of these pathways for modulating CFTR activity and thereby mucus hydration. We used RT-PCR and/or Western blot to determine connexin (Cx), CD73 and EP-R expression in the Calu-3 airway epithelial cell line ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=3291408 Thu, 18 Feb 2010 00:00:00 +0100 3291408 http://www.medworm.com/index.php?rid=3255299&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%3D20139349%26dopt%3DAbstract Authors: Langsdorf A, Radzikinas K, Kroten A, Jain S, Ai X Our study investigates the innervation of the respiratory tract during mouse embryonic development with a focus on identification of cell origin and essential developmental signals for the resident, or intrinsic, neurons. Using lineage tracing, we show that these intrinsic neurons are exclusively derived from neural crest cells and cluster to form ganglia that reside in the dorsal trachea and medial bronchi with diminishing frequency. Comparison of intrinsic neurogenesis between wildtype, GDNF-/-, NRTN-/- and Ret-/- embryos, in combination with lung organ cultures, has identified that Ret signaling, redundantly activated by GDNF family members, is required for intrinsic neurogenesis in the trachea and primary bronchi. In contra... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=3255299 Fri, 05 Feb 2010 00:00:00 +0100 3255299 http://www.medworm.com/index.php?rid=3255298&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%3D20139350%26dopt%3DAbstract In this study, the effects of NO on sodium reabsorption by H441 cell monolayers were studied in an Ussing chamber. Two NO donors, (Z)-1-[N-(3-aminopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate (papaNONOate) and diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (deaNONOate), rapidly, reversibly and dose-dependently reduced amiloride-sensitive short circuit currents across H441 cell monolayers. This effect was neutralized by the NO scavenger hemoglobin, and was not observed with inactive NO donors. The effects of NO were not blocked by 8 bromoguanosine-3',5'-cyclic monophosphate or by soluble guanylate cyclase (sGC) inhibitors (methylene blue and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), and were, therefore, independent of sGC signaling. NO targeted apical, highly-sel... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=3255298 Fri, 05 Feb 2010 00:00:00 +0100 3255298 http://www.medworm.com/index.php?rid=3255297&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%3D20139351%26dopt%3DAbstract Authors: Mirzapoiazova T, Moitra J, Moreno-Vinasco L, Sammani S, Turner JR, Chiang ET, Evenoski C, Wang T, Singleton PA, Huang Y, Lussier YA, Watterson DM, Dudek SM, Garcia JG Acute lung injury (ALI) and mechanical ventilator-induced lung injury (VILI), major causes of acute respiratory failure with elevated morbidity and mortality, are characterized by significant pulmonary inflammation and alveolar/vascular barrier dysfunction. Prior studies have highlighted the role of the non-muscle myosin light chain kinase isoform (nmMLCK) as an essential element of the inflammatory response with variants in the MYLK gene which contribute to ALI susceptibility. To further define nmMLCK involvement in acute inflammatory syndromes, we utilized two murine models of inflammatory lung injury induced b... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=3255297 Fri, 05 Feb 2010 00:00:00 +0100 3255297 http://www.medworm.com/index.php?rid=3172488&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%3D20068226%26dopt%3DAbstract Authors: Brody AR PMID: 20068226 [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=3172488 Thu, 14 Jan 2010 22:44:10 +0100 3172488 http://www.medworm.com/index.php?rid=3172487&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%3D20068227%26dopt%3DAbstract Authors: Heintz NH, Janssen-Heininger YM, Mossman BT Fifteen years have passed since we published findings in the AJRCMB demonstrating that induction of early response fos/jun proto-oncogenes in rodent tracheal and mesothelial cells correlates with fibrous geometry and pathogenicity of asbestos. Our study was the first to suggest that the aberrant induction of signaling responses by crocidolite asbestos and erionite, a fibrous zeolite mineral associated with the development of malignant mesotheliomas (MMs) in areas of Turkey, led to altered gene expression. New data questioned the widely held belief at that time that the carcinogenic effects of asbestos in the development of lung cancer and MM were due to genotoxic or mutagenic effects. Later studies by our group revealed that proto-on... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=3172487 Thu, 14 Jan 2010 22:44:05 +0100 3172487 http://www.medworm.com/index.php?rid=3164452&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%3D20061511%26dopt%3DAbstract Authors: Pechkovsky DV, Hackett TL, An SS, Shaheen F, Murray LA, Knight DA Given the contribution various fibroblast subsets make to wound healing and tissue remodeling, the concept of lung fibroblast heterogeneity is of great scientific interest. However, the mechanisms contributing to this heterogeneity are unknown. To this aim, we compared molecular and biophysical characteristics of fibroblasts concurrently isolated from normal human proximal bronchi (B-FBR) and distal lung parenchyma (P-FBR). Using quantitative RT-PCR, spontaneous expression of more than 30 genes related to repair and remodeling was analyzed. All P-FBR lines demonstrated significantly increased basal alphaSMA mRNA and protein expression levels when compared with donor-matched B-FBR. These differences were not asso... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=3164452 Fri, 08 Jan 2010 00:00:00 +0100 3164452 http://www.medworm.com/index.php?rid=3114927&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%3D20026648%26dopt%3DAbstract Authors: Eickelberg O, Laurent GJ PMID: 20026648 [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=3114927 Wed, 23 Dec 2009 16:18:07 +0100 3114927 http://www.medworm.com/index.php?rid=3114926&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%3D20026649%26dopt%3DAbstract Authors: Kreisel D PMID: 20026649 [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=3114926 Wed, 23 Dec 2009 16:18:04 +0100 3114926 http://www.medworm.com/index.php?rid=3075805&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%3D19995942%26dopt%3DAbstract Authors: Ormiston ML, Deng Y, Stewart DJ, Courtman DW Direct injection of endothelial progenitor cells (EPCs) into the circulation has shown therapeutic benefit in both experimental models and clinical studies of pulmonary arterial hypertension (PAH). Using the monocrotaline (MCT)-induced rat model of PAH, we investigated the role of innate immunity in the therapeutic activity of two types of putative EPCs derived from human peripheral blood mononuclear cells: an early population of endothelial-like, culture modified monocytes (E-CMMs) and late-outgrowth EPCs (L-EPCs), which exhibit a strong endothelial phenotype. In the athymic nude rat, E-CMMs prevented monocrotaline (MCT)-induced increases in right ventricular systolic pressure (P<0.001) and right ventricular hypertrophy (P<0.... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=3075805 Mon, 07 Dec 2009 00:00:00 +0100 3075805 http://www.medworm.com/index.php?rid=3075804&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%3D19995943%26dopt%3DAbstract Authors: Albaiceta GM, Gutierrez-Fernandez A, Garcia-Prieto E, Puente XS, Parra D, Astudillo A, Campestre C, Cabrera S, Gonzalez-Lopez A, Fueyo A, Taboada F, Lopez-Otin C Mechanical ventilation is a life-saving therapy that can also damage the lungs. Ventilator-induced lung injury promotes inflammation and upregulates matrix metalloproteinases (MMPs). Among these enzymes, MMP-8 is involved in the onset of inflammation by processing different immune mediators. To clarify the role of MMP-8 in a model of ventilator-induced lung injury and their relevance as a therapeutic target, we ventilated wildtype and MMP-8 deficient mice using low or high pressures for two hours. There were no significant differences after low pressure ventilation between wildtype and knockout animals. However, lack ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=3075804 Mon, 07 Dec 2009 00:00:00 +0100 3075804 http://www.medworm.com/index.php?rid=2918236&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%3D19843709%26dopt%3DAbstract Authors: Adler KB, Matalon S PMID: 19843709 [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=2918236 Fri, 23 Oct 2009 13:36:08 +0100 2918236 http://www.medworm.com/index.php?rid=2918235&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%3D19843710%26dopt%3DAbstract Authors: Aoshiba K, Nagai A PMID: 19843710 [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=2918235 Fri, 23 Oct 2009 13:36:05 +0100 2918235 http://www.medworm.com/index.php?rid=2918251&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%3D19843704%26dopt%3DAbstract Authors: Wong CK, Hu S, Cheung PF, Lam CW Thymic stromal lymphopoietin (TSLP) is highly expressed by bronchial epithelial cells and skin keratinocytes in allergic diseases. TSLP acts as a master switch for allergic inflammation through the activation of dendritic cells and mast cells for initiating inflammatory type 2 T-helper lymphocyte (Th2) responses. To elucidate the immunological cascades of epithelium/keratinocyte-eosinophil mediated allergic inflammation, we examined the modulating effects of TSLP on human eosinophils. Expression of TSLP receptor complex was detected by RT-PCR, flow cytometry and Western blot. Adhesion molecules, cytokine and chemokines were quantitated by flow cytometry or ELISA. Intracellular signal transduction molecules were measured by Western blot and flow... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2918251 Mon, 19 Oct 2009 23:00:00 +0100 2918251 http://www.medworm.com/index.php?rid=2918244&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%3D19843705%26dopt%3DAbstract Authors: Spiess PC, Morin D, Williams CR, Buckpitt AR Naphthalene is a semi-volatile aromatic hydrocarbon to which humans are exposed from a variety of sources. Naphthalene results in acute cytotoxicity to respiratory epithelium in rodents. Cytochrome P450-dependent metabolic activation to form reactive intermediates and loss of soluble cellular thiols (glutathione) are critical steps in naphthalene toxicity, but the precise mechanisms by which this chemical results in cellular injury remain unclear. Protein thiols are likely targets of reactive naphthalene metabolites. Loss of these, either through adduction or thiol oxidation mechanisms, may be important underlying mechanisms for naphthalene toxicity. To address the hypothesis that loss of thiols on specific cellular proteins is crit... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2918244 Mon, 19 Oct 2009 23:00:00 +0100 2918244 http://www.medworm.com/index.php?rid=2918239&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%3D19843706%26dopt%3DAbstract Authors: Burnham EL, Mealer M, Gaydos J, Majka S, Moss M Acute lung injury (ALI) and severe sepsis are common critical illnesses associated with mobilization of bone marrow-derived cells into circulation. By identifying and determining these cellsâ functional characteristics, unique prognostic biomarkers can be developed to help investigators understand mechanisms underlying the pathophysiology of these disorders. We previously demonstrated increased colony forming unit (CFU) ability of circulating peripheral blood mononuclear cells (PBMCs) from patients with ALI compared to healthy controls that also correlated with improved survival. Here we hypothesized that increased CFUs observed in ALI are associated with lung injury, and therefore ALI will result in an increased number of C... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2918239 Mon, 19 Oct 2009 23:00:00 +0100 2918239 http://www.medworm.com/index.php?rid=2918238&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%3D19843707%26dopt%3DAbstract Authors: Gueders MM, Hirst SJ, Quesada-Calvo F, Paulissen G, Hacha J, Gilles C, Gosset P, Louis R, Foidart JM, Lopez-Otin C, Noël A, Cataldo DD Matrix metalloproteinases (MMPs) recently appeared as key regulators of inflammation, allowing recruitment and clearance of inflammatory cells and modifying the biological activity of many peptidic mediators by cleavage. MMP-19 is a newly described MMP and preferentially cleaves matrix proteins such as collagens and tenascin-C. The role of MMP-19 in asthma has not been described to date. The purpose of the present study was to assess MMP-19 expression in a murine asthma model and to address biological effects of MMP-19 deficiency in mice. Allergen-exposed wild-type (WT) mice displayed an increased expression of MMP-19 mRNA and an increased... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2918238 Mon, 19 Oct 2009 23:00:00 +0100 2918238 http://www.medworm.com/index.php?rid=2918237&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%3D19843708%26dopt%3DAbstract This study examined the expression and function of transient receptor potential (TRP) channels in human macrophages. Human alveolar macrophages and lung tissue macrophages expressed increased mRNA and protein for TRPC6 when compared with monocytes and monocyte-derived-macrophages. Moreover, TRPC6 mRNA expression was significantly elevated in alveolar macrophages from COPD patients compared to control subjects. There were no differences in mRNA for TRPC3 or TRPC7. Although mRNA for TRPM2 and TRPV1 was detected in these cells, protein expression could not be determined. Fractionation of lung derived-macrophages demonstrated that TRPC6 protein was more highly expressed by smaller macrophages compared with larger macrophages. Using whole-cell patch clamp electrophysiology, TRPC6-like currents ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2918237 Mon, 19 Oct 2009 23:00:00 +0100 2918237 http://www.medworm.com/index.php?rid=2847305&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%3D19783786%26dopt%3DAbstract In this study we sought, firstly, to determine whether HRV infection modulated the expression of MMP-9 and its highest affinity inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1 and, secondly, to explore the mechanism by which this occurs. In vitro studies, using RT-PCR, ELISA, zymography and a fluorescent activity assay, demonstrated that MMP-9 mRNA, protein and activity were increased upon infection with HRV, while TIMP-1 mRNA and protein remained unchanged. These results were then verified in vivo, using nasal lavage samples obtained from subjects with confirmed rhinovirus infections. HRV infections have been shown to upregulate NF-kappaB, and NF-kappaB has also been reported to play a role in MMP-9 expression. We therefore investigated the role of NF-kappaB in HRV-induced MMP-9... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2847305 Thu, 24 Sep 2009 23:00:00 +0100 2847305 http://www.medworm.com/index.php?rid=2847304&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%3D19783787%26dopt%3DAbstract In this study we have identified a Pneumocystis beta-1,3-endoglucanase gene (PCEng2) that is demonstrated to play a significant role in cell wall regulation. The full sequence of the gene revealed a 2.2kb open reading frame with conserved amino acid domains homologous to similar fungal glycosyl hydrolases (GH family 81). The gene transcript showed upregulation in cystic isolates and the expressed protein was detected within both cyst and trophic forms. Complementation assays in Eng2 deleted S. cerevisiae strains showed restoration of the cell wall separation defect during proliferation, demonstrating the importance of PCEng2p during fungal growth. These findings suggest that regulation of cyst cell wall beta-glucans is a fundamental process during completion of the Pneumocystis carinii lif... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2847304 Thu, 24 Sep 2009 23:00:00 +0100 2847304 http://www.medworm.com/index.php?rid=2847303&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%3D19783788%26dopt%3DAbstract Conclusions: This study shows that epithelial infection with RV induces a decrease of ss2AR function on airway smooth muscle cells, potentially explaining the clinical observation of loss of ss2AR agonist function during RV-induced asthma exacerbations. PMID: 19783788 [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=2847303 Thu, 24 Sep 2009 23:00:00 +0100 2847303 http://www.medworm.com/index.php?rid=2847302&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%3D19783789%26dopt%3DAbstract Authors: Cooper PR, Poll CT, Barnes PJ, Sturton RG Chronic obstructive pulmonary disease (COPD) involves disease of small airways with an increase in airway smooth muscle sensitivity to spasmogens and with structural changes described as airway remodeling. We have investigated the effect tobacco smoke (TS) exposure on the structure and function of small airways in rats, and have also studied the role of interleukin (IL)-13 in this response. Precision-cut lung slices (230-280 microm) were prepared from male Sprague-Dawley rats after acute (3 days) or chronic (8 or 16 weeks) daily exposure to TS, or air. Carbachol (CCh) and 5-hydroxytryptamine (5HT) concentration-responses were performed on airways (50-400 microm diameter). The effect of IL-13 in vitro on small airway sensitivity to CCh ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2847302 Thu, 24 Sep 2009 23:00:00 +0100 2847302 http://www.medworm.com/index.php?rid=2847301&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%3D19783790%26dopt%3DAbstract Authors: Msiska Z, Pacurari M, Mishra A, Leonard SS, Castranova V, Vallyathan V DNA double strand breaks (DNA DSBs) are a very rapid response to DNA damage that occurs in cells subjected to radiation, exposure to toxic substances, and other environmental stresses. The inability to repair these breaks can lead to carcinogenesis. One of the earliest responses to DNA DSBs is the phosphorylation of a histone, H2AX, at serine 139, yielding a focal product (gamma-H2AX) that can be detected by a fluorescent antibody. A study was undertaken to compare the induction of DNA DSBs in normal (SAE) and cancer cells (A549) after exposure to asbestos (crocidolite), a proven carcinogen, silica a suspected carcinogen, and titanium dioxide (an inert particle, recently reported to be carcinogenic in anima... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2847301 Thu, 24 Sep 2009 23:00:00 +0100 2847301 http://www.medworm.com/index.php?rid=2782579&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%3D19738159%26dopt%3DAbstract Authors: Cesta MF, Ryman-Rasmussen JP, Wallace DG, Masinde T, Hurlburt G, Taylor AJ, Bonner JC Engineered multi-walled carbon nanotubes (MWCNT) represent a possible health risk for pulmonary fibrosis due to their fiber-like shape and potential for persistence in the lung. We postulated that bacterial lipopolysaccharide (LPS), a ubiquitous agent in the environment that causes lung inflammation, would enhance fibrosis caused by MWCNT. Rats were exposed to LPS and then intratracheally instilled with MWCNT or carbon black (CB) nanoparticles 24 hrs later. Pulmonary fibrosis was observed 21 days post-MWCNT exposure, but not with CB. LPS alone caused no fibrosis but enhanced MWCNT-induced fibrosis. LPS plus CB did not significantly increase fibrosis. MWCNT increased platelet-derived growth fa... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2782579 Mon, 07 Sep 2009 23:00:00 +0100 2782579 http://www.medworm.com/index.php?rid=2782578&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%3D19738160%26dopt%3DAbstract Authors: Balamayooran G, Batra S, Fessler MB, Happel KI, Jeyaseelan S Bacterial lung diseases are a major cause of morbidity and mortality both in immunocompromised and immunocompetent individuals. Neutrophil accumulation, a pathological hallmark of bacterial diseases, is critical to host defense, but may also cause ALI/ARDS. Toll-like receptors, NOD-like receptors, transcription factors, cytokines, and chemokines play essential roles in neutrophil sequestration in the lungs. This review highlights our current understanding of the role of these molecules in the lungs during bacterial infection and their therapeutic potential. We also discuss emerging data on cholesterol and ethanol as environmentally modifiable factors that may impact neutrophilmediated pulmonary innate host defense. U... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2782578 Mon, 07 Sep 2009 23:00:00 +0100 2782578 http://www.medworm.com/index.php?rid=2782577&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%3D19738161%26dopt%3DAbstract Authors: Vadivel A, Abozaid S, van Haaften T, Sawicka M, Eaton F, Chen M, Thebaud B Bronchopulmonary dysplasia (BPD) and emphysema are significant global health problems at the extreme stages of life. Both are characterized by alveolar simplification and abnormal distal airspace enlargement due to arrested development or loss of alveoli, respectively. Both lack effective treatments. Mechanisms that inhibit distal lung growth are poorly understood. Adrenomedullin (AM), a recently discovered potent vasodilator, promotes angiogenesis and has protective effects on the cardiovascular and respiratory system. Its role in the developing lung is unknown. We hypothesized that AM promotes lung angiogenesis and alveolar development. Accordingly, we report that lung mRNA expression of AM increases ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2782577 Mon, 07 Sep 2009 23:00:00 +0100 2782577 http://www.medworm.com/index.php?rid=2752476&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%3D19717810%26dopt%3DAbstract Authors: Barnes PJ Multiple cytokines play a role in the orchestration of inflammation in inflammatory airway diseases, such as COPD, through the recruitment, activation and survival of inflammatory cells. Lymphokines secreted from T-cells regulate the pattern of inflammation, whereas proinflammatory cytokines amplify and perpetuate the inflammatory response. Multiple chemokines recruit inflammatory cells from the circulation into the lungs and many growth factors maintain this inflammation and lead to characteristic structural changes in the airways. There are several therapeutic approaches that target cytokine-mediated inflammation in COPD, but blocking specific cytokines may not provide clinical benefit, whereas broad-spectrum anti-inflammatory approaches are more likely to be of cl... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2752476 Thu, 27 Aug 2009 23:00:00 +0100 2752476 http://www.medworm.com/index.php?rid=2752475&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%3D19717811%26dopt%3DAbstract Authors: Ross B, D'Orleans-Juste P, Giaid A Endothelin-1 (ET-1) plays a central role in lung fibrosis. It is released in the lung at low concentrations from the endothelium, epithelium and vascular smooth muscle cells and orchestrates a variety of effects.1, 2 In the context of wound healing, ET-1 acts with other profibrotic mediators to recruit fibroblasts and allow for their differentiation to contractile myofibroblasts.3 These specialized cells in turn lay down fibrotic tissue and contract at the site of lesions to restore tissue integrity. Apoptosis and reversion to quiescence ensues.4 However, in diseases of the lung such as idiopathic pulmonary fibrosis (IPF), the fibrotic response is uncontrolled. Progressive injury to lung tissue, isolated both temporally and geographically, is... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2752475 Thu, 27 Aug 2009 23:00:00 +0100 2752475 http://www.medworm.com/index.php?rid=2752474&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%3D19717812%26dopt%3DAbstract Authors: Potter-Perigo S, Johnson PY, Evanko SP, Chan CK, Braun KR, Wilkinson TS, Altman LC, Wight TN Viral infections are known to exacerbate asthma and other lung diseases where chronic inflammatory processes are implicated, but the mechanism is not well understood. The viral mimetic, polyinosine-polycytidylic acid (poly I:C), causes accumulation of a versican- and hyaluronan-enriched extracellular matrix (ECM) by human lung fibroblasts (HLF) with increased capacity for monocyte adhesion. The 5-fold increase in versican retention in this ECM is due to altered compartmentalization with decreased degradation of cell-layer associated versican rather than an increase in total accumulation in the culture. This is consistent with decreased mRNA levels for all of the versican splice variant... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2752474 Thu, 27 Aug 2009 23:00:00 +0100 2752474 http://www.medworm.com/index.php?rid=2752473&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%3D19717813%26dopt%3DAbstract Authors: Hogmalm A, Sheppard D, Lappalainen U, Bry K Pulmonary inflammation is associated with the development of bronchopulmonary dysplasia (BPD) in premature infants. We have previously shown that perinatal pulmonary expression of human interleukin-1beta (IL-1beta) is sufficient to cause a lung disease similar to BPD, characterized by inflammation, impaired alveolarization, poor postnatal growth, and increased mortality in infant mice. The alphavbeta6 integrin plays a critical role in regulating inflammation in the adult lung. To study the role of the beta6 integrin subunit in neonatal inflammatory lung disease, we compared the pulmonary development in IL-1beta-expressing infant mice with wildtype or null beta6 integrin loci. Absence of the beta6 integrin subunit decreased the mortal... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2752473 Thu, 27 Aug 2009 23:00:00 +0100 2752473 http://www.medworm.com/index.php?rid=2752472&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%3D19717814%26dopt%3DAbstract Authors: Goolaerts A, Roux J, Ganter MT, Shlyonsky V, Chraibi A, Stéphane R, Mies F, Matthay MA, Naeije R, Sariban-Sohraby S, Howard M, Pittet JF Hypoxia and epithelial stretch that are commonly observed in patients with acute lung injury have been shown to promote the release of serotonin in vitro. However, whether serotonin contributes to the decrease of the alveolar epithelial fluid transport, which is a hallmark of lung injury, is unknown. Thus, we investigated the effect of serotonin on ion and fluid transport across the alveolar epithelium. Serotonin caused a dose-dependent inhibition of the amiloride-sensitive current across primary rat and human alveolar epithelial (ATII) cell monolayers, but did not affect Na+/K+ ATPase function. Furthermore, we found that the serotonin-i... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2752472 Thu, 27 Aug 2009 23:00:00 +0100 2752472 http://www.medworm.com/index.php?rid=2752471&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%3D19717815%26dopt%3DAbstract Conclusions: p38 modulates cytokine induced skeletal muscle caspase activation. PMID: 19717815 [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=2752471 Thu, 27 Aug 2009 23:00:00 +0100 2752471 http://www.medworm.com/index.php?rid=2668556&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%3D19648471%26dopt%3DAbstract Authors: White TA, Witt TA, Pan S, Mueske CS, Kleppe LS, Holroyd EW, Champion HC, Simari RD Pulmonary hypertension (PH) is a commonly recognized complication of chronic respiratory disease. Enhanced vasoconstriction, pulmonary vascular remodeling and in situ thrombosis contribute to the increased pulmonary vascular resistance observed in PH associated with hypoxic lung disease. The tissue factor pathway regulates fibrin deposition in response to acute and chronic vascular injury. We hypothesized that inhibition of the tissue factor pathway would result in attenuation of pathophysiologic parameters typically associated with hypoxiainduced PH. We tested this hypothesis using a chronic hypoxia-induced murine model of PH utilizing mice that overexpress tissue factor pathway inhibitor (TFPI... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2668556 Thu, 30 Jul 2009 23:00:00 +0100 2668556 http://www.medworm.com/index.php?rid=2668555&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%3D19648472%26dopt%3DAbstract Authors: Ahmad T, Mabalirajan U, Ghosh B, Agrawal A Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), causes uncoupling of NOS leading to generation of reactive nitrogen species such as peroxynitrite. The lung generates a significant amount of ADMA, potentially contributing to plasma ADMA levels that have been related to endothelial dysfunction. ADMA infusion causes increased collagen deposition in lungs, suggesting that it could influence the development of chronic lung diseases such as fibrosis, COPD, and asthma. To explore the link between endogenous ADMA and asthma, we determined the levels of ADMA, enzymes implicated in its metabolism and peroxynitrite in murine models of allergic airway inflammation (AAI) resembling asthma. ADMA levels an... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2668555 Thu, 30 Jul 2009 23:00:00 +0100 2668555 http://www.medworm.com/index.php?rid=2668554&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%3D19648473%26dopt%3DAbstract Conclusions: TRPC3 is an important molecular component of native NSCCs contributing to the resting Vm and [Ca2+]i in normal ASMCs, as well as membrane depolarization and hyperresponsiveness in ovalbumin-sensitized/challenged cells, whereas TRPC1-encoded NSCCs are only activated in ovalbumin-sensitized/challenged airway myocytes. PMID: 19648473 [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=2668554 Thu, 30 Jul 2009 23:00:00 +0100 2668554 http://www.medworm.com/index.php?rid=2668553&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%3D19648474%26dopt%3DAbstract Authors: Griesenbach U, Sumner-Jones SG, Holder E, Munkonge FM, Wodehouse T, Smith SN, Wasowicz MY, Pringle I, Casamayor I, Chan M, Coles R, Cornish N, Dewar A, Doherty A, Farley R, Green AM, Jones BL, Larsen MD, Lawton AE, Manvell M, Painter H, Singh C, Somerton L, Stevenson B, Varathalingam A, Siegel C, Scheule RK, Cheng SH, Davies JC, Porteous DJ, Gill DR, Boyd AC, Hyde SC, Alton EW A clinical programme to assess whether lipid GL67A-mediated gene-transfer can ameliorate cystic fibrosis (CF) lung disease is currently being undertaken by the UKCF Gene Therapy Consortium. We have evaluated GL67A gene transfer to the murine nasal epithelium of wildtype and CF knockout mice to assess this tissue as a test site for gene transfer agents. The plasmids used were regulated by either (a) the c... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2668553 Thu, 30 Jul 2009 23:00:00 +0100 2668553 http://www.medworm.com/index.php?rid=2668552&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%3D19648475%26dopt%3DAbstract In conclusion, mechanical stretch activates Ca(2+) influx via stretch-activated channels different from other Ca(2+) influx pathways such as receptor- and store-operated Ca(2+) entries in HPMVECs that is tightly regulated by the actin cytoskeleton. These results suggest that abnormal Ca(2+) homeostasis due to excessive mechanical stretch during mechanical ventilation may play a role in ALI/ARDS progression. PMID: 19648475 [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=2668552 Thu, 30 Jul 2009 23:00:00 +0100 2668552 http://www.medworm.com/index.php?rid=2668551&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%3D19648476%26dopt%3DAbstract We examined the contribution of p70 ribosomal S6 kinase (p70S6K) to airway smooth muscle hypertrophy, a structural change found in asthma. In human airway smooth muscle cells, transforming growth factor (TGF)-beta, endothelin-1 and cardiotrophin-1 each induced phosphorylation of p70S6K and ribosomal protein S6 while increasing cell size, total protein synthesis and relative protein abundance of alpha-smooth muscle actin and SM22. Transfection of myocytes with siRNA against either p70S6K or S6, or infection with retrovirus encoding a kinase-dead p70S6K, reduced cell size and protein synthesis but had no effect on contractile protein expression per mg total protein. Infection with a retrovirus encoding a constitutively active, rapamycin resistant (RR) p70S6K increased cell size but not contr... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2668551 Thu, 30 Jul 2009 23:00:00 +0100 2668551 http://www.medworm.com/index.php?rid=2654256&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%3D19635928%26dopt%3DAbstract Conclusion: These findings employing several structurally different Asm inhibitors identify Asm as primary target in the lung to reduce ceramide concentrations. Inhaling an Asm inhibitor may be a beneficial treatment for CF, with minimal adverse systemic effects. PMID: 19635928 [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=2654256 Sun, 26 Jul 2009 23:00:00 +0100 2654256 http://www.medworm.com/index.php?rid=2654255&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%3D19635929%26dopt%3DAbstract Conclusions: This study illustrates that superoxide scavengers increase upper airway muscle force and that this effect persists under hypoxic conditions. We conclude that antioxidant treatment may be beneficial as a therapy in obstructive sleep apnoea. PMID: 19635929 [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=2654255 Sun, 26 Jul 2009 23:00:00 +0100 2654255 http://www.medworm.com/index.php?rid=2654254&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%3D19635930%26dopt%3DAbstract We report elevated levels of soluble (s)TRAIL released by leukocytes in bronchoalveolar lavage fluid (BALF) of patients with RSV-associated respiratory failure (n=22) as compared to mechanically ventilated patients without pulmonary illness (n=7). Primary bronchial epithelial cells of children without pulmonary disease obtained by non-bronchoscopic cytobrushing expressed both death receptors TRAIL-R1 and -R2, and were found to be susceptible for cell death by human recombinant sTRAIL in vitro. Furthermore, BALF from a RSV patient induced cell death in these cells, which was partly attenuated by inhibiting TRAIL signaling. These data suggest that the TRAIL pro-apoptotic pathway may contribute to lung epithelial injury in severe RSV infection in children. PMID: 19635930 [PubMed - as supp... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2654254 Sun, 26 Jul 2009 23:00:00 +0100 2654254 http://www.medworm.com/index.php?rid=2654253&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%3D19635931%26dopt%3DAbstract Authors: Wyatt TA, Slager RE, Heires AJ, Devasure JM, Von Essen SG, Poole JA, Romberger DJ Rationale: Dust samples collected from Nebraska swine confinement facilities (hog dust extract, HDE) are known to elicit proinflammatory cytokine release from human bronchial epithelial (HBE) cells in vitro. This response involves the activation of two protein kinase C isoforms (PKCalpha and PKCepsilon). Experiments were designed to investigate the relationship between the two isoenzymes and the degree to which each is responsible for cytokine release in HBE. Experiments also examined the contribution of tumor necrosis factor alpha (TNFalpha) to interleukin (IL)-6 and IL-8 release. Methods: PKCalpha and PKCepsilon activities were inhibited using isoform-specific pharmacologic inhibitors and genet... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2654253 Sun, 26 Jul 2009 23:00:00 +0100 2654253 http://www.medworm.com/index.php?rid=2654252&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%3D19635932%26dopt%3DAbstract Authors: Tucker TA, Dean C, Komissarov A, Koenig K, Mazar A, Pendurthi U, Allen TC, Idell S ABSTRACT Malignant pleural mesothelioma (MPM) is a lethal neoplasm for which current therapy is unsatisfactory. The urokinase plasminogen activator receptor (uPAR) is associated with increased virulence of many solid neoplasms but its role in the pathogenesis of MPM is currently unclear. We found that REN human pleural MPM cells expressed 4-10-fold more uPAR than MS-1 or M9K MPM cells or MeT5A human pleural mesothelial cells. In a new orthotopic murine model of MPM, we found that the kinetics of REN cell tumorigenesis is accelerated versus MS-1 or M9K cells, that REN instillates generated larger tumors expressing increased uPAR, were more invasive and caused earlier mortality. While REN, MS-1 an... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2654252 Sun, 26 Jul 2009 23:00:00 +0100 2654252 http://www.medworm.com/index.php?rid=2654251&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%3D19635933%26dopt%3DAbstract Authors: Hardy CL, Lemasurier JS, Olsson F, Dang T, Yao J, Yang M, Plebanski M, Phillips DJ, Mollard RA, Rolland JM, O'Hehir R Activin A is a member of the TGF-beta superfamily and plays a role in allergic inflammation and asthma pathogenesis. Recent evidence suggests that activin A regulates pro-inflammatory cytokine production and is itself regulated by inflammatory mediators. In a murine model of acute allergic airway inflammation, we observed previously that increased activin A concentrations in bronchoalveolar lavage fluid coincide with Th2 cytokine production in lung-draining lymph nodes and pronounced mucus metaplasia in bronchial epithelium. We therefore hypothesised that IL-13, the key cytokine for mucus production, regulates activin A secretion into bronchoalveolar lavage flu... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2654251 Sun, 26 Jul 2009 23:00:00 +0100 2654251 http://www.medworm.com/index.php?rid=2602940&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%3D19597126%26dopt%3DAbstract This study aims to investigate early S. aureus impact on chemokine secretion by CF epithelial cells and chemotaxis of CF T cells. CF and non-CF AEC were grown in a cell culture model and apically stimulated with S.aureus. Supernatants were quantified for chemokine secretions and assayed for T cell chemotaxis. CF AEC were found to secrete constitutively larger amounts of IL-8, GROalpha, MIG, MIP-3beta and MCP-1 than non-CF epithelial cells. However, S. aureus interaction with epithelial cells increased chemokine production by non-CF cells, whereas it had no effect on CF cells. Interestingly, chemotaxis of T cells derived from CF patients was greater than that of non-CF patient T cells. Moreover, there were more CF T cells expressing CXCR1 as compared to non-CF T cells. Indeed, under our exp... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2602940 Sun, 12 Jul 2009 23:00:00 +0100 2602940 http://www.medworm.com/index.php?rid=2602939&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%3D19597127%26dopt%3DAbstract In conclusion, the hallmark of IPF/UIP histopathology, the fibroblast focus, consists of differentiated, quiescent cells that are prominently expressing GATA-6. PMID: 19597127 [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=2602939 Sun, 12 Jul 2009 23:00:00 +0100 2602939 http://www.medworm.com/index.php?rid=2602938&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%3D19597128%26dopt%3DAbstract Authors: Koarai A, Sugiura H, Yanagisawa S, Ichikawa T, Minakata Y, Matsunaga K, Hirano T, Akamatsu K, Ichinose M Virus infections are a major cause of COPD exacerbations. Recently, toll-like receptor 3 (TLR3) has been demonstrated to react to double-stranded RNA (dsRNA) and to be involved in the immune responses after viral infections. In the present study, we examined whether oxidative stress, which is involved in the pathogenesis of COPD, enhances the responses of TLR3 in airway epithelial cells. The effect of hydrogen peroxide (H2O2) on the release of IL-8 from BEAS-2B cells and primary human bronchial epithelial cells after stimulation with polyinosine-polycytidylic acid [poly(I:C)], a synthetic analog of viral dsRNA and aãligand for TLR3, and the signal transduction were exa... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2602938 Sun, 12 Jul 2009 23:00:00 +0100 2602938 http://www.medworm.com/index.php?rid=2549132&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%3D19525385%26dopt%3DAbstract Authors: Powell CA PMID: 19525385 [PubMed - indexed for MEDLINE] (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=2549132 Sun, 28 Jun 2009 06:44:23 +0100 2549132 http://www.medworm.com/index.php?rid=2549128&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%3D19541845%26dopt%3DAbstract Authors: Reynolds PR, Schmitt RE, Kasteler SD, Sturrock A, Sanders K, Bierhaus A, Nawroth PP, Paine Iii R, Hoidal JR Patients with acute lung injury (ALI) almost always require supplemental oxygen during treatment; however, elevated oxygen itself is toxic. Receptors for advanced glycation end-products (RAGE) are multiligand cell surface receptors predominantly localized to alveolar type I (ATI) cells that influence development and cigarette smoke-induced inflammation, but studies that address the role of RAGE in ALI are insufficient. In the present investigation, we test the hypothesis that RAGE signaling functions in hyperoxia-induced inflammation. RAGE null mice exposed to hyperoxia survived 3 days longer than age-matched wild-type mice. After four days in hyperoxia, RAGE null mice h... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2549128 Wed, 24 Jun 2009 23:00:00 +0100 2549128 http://www.medworm.com/index.php?rid=2549127&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%3D19556602%26dopt%3DAbstract In conclusion our data demonstrate that S1P signalling is involved in the complex pathway underlying airway hyper-responsiveness. PMID: 19556602 [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=2549127 Wed, 24 Jun 2009 23:00:00 +0100 2549127 http://www.medworm.com/index.php?rid=2549126&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%3D19556603%26dopt%3DAbstract This study establishes an important in vitro model that facilitates mechanistic studies of Cr(VI)-induced carcinogenesis, and elucidates a novel mechanism that causes apoptosis-resistant malignant transformation of non-tumorigenic lung cells in response to a human carcinogen. PMID: 19556603 [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=2549126 Wed, 24 Jun 2009 23:00:00 +0100 2549126 http://www.medworm.com/index.php?rid=2549125&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%3D19556604%26dopt%3DAbstract We reported that lung adenocarcinoma cell lines from female, but not male, NSCLC patients respond proliferatively and transcriptionally to estradiol (E2), despite equal protein expression of estrogen receptors alpha and beta (ERalpha and ERbeta). To test the hypothesis that nuclear localization of ERalpha corresponds to genomic E2 activity in lung adenocarcinoma cells from females, cell fractionation, immunoblot, and confocal immunohistochemical microscopy were performed. We report for the first time that E2 increases phospho-serine-118-ERalpha (P-ser118-ERalpha ) and cyclin D1 nuclear colocalization in H1793 but not A549 lung adenocarcinoma cells derived from a female and male patient, respectively. ERalpha was primarily in the cytoplasm and mitochondria, independent of E2 treatment, and ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2549125 Wed, 24 Jun 2009 23:00:00 +0100 2549125 http://www.medworm.com/index.php?rid=2549124&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%3D19556605%26dopt%3DAbstract Authors: Kettle R, Simmons J, Schindler F, Jones P, Dicker T, Dubois G, Giddings J, Van Heeke G, Jones CE Excessive mucus production has been linked to many of the pathological features of respiratory diseases including obstruction of the airways, decline in lung function, increased rates of mortality and increased infections. The mucins MUC5AC and MUC5B contribute to the viscoelastic properties of mucus and are found at elevated levels in the airways of individuals with chronic respiratory diseases. The Th2 cell cytokine interleukin-13 (IL-13) is known to regulate MUC5AC expression in goblet cells of the airways, though much less is known about the regulation of MUC5B expression. In a study to further understand the mediators of MUC5AC and MUC5B expression, NRG1beta1 was identified as... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2549124 Wed, 24 Jun 2009 23:00:00 +0100 2549124 http://www.medworm.com/index.php?rid=2549123&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%3D19556606%26dopt%3DAbstract In conclusion, genetic removal of A2B adenosine receptors in mice leads to inhibition of allergen-induced chronic pulmonary inflammation and airway remodeling. These findings are in agreement with previous pharmacological studies suggesting a deleterious role for A2B receptor signaling in chronic lung inflammation. PMID: 19556606 [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=2549123 Wed, 24 Jun 2009 23:00:00 +0100 2549123 http://www.medworm.com/index.php?rid=2549131&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%3D19541842%26dopt%3DAbstract Authors: Kuhn AR, Schlauch K, Lao R, Halayko AJ, Gerthoffer WT, Singer CA Mechanisms by which differentiated, contractile smooth muscle cells become proliferative and secretory is one way airway smooth muscle (ASM) cells respond to mechanical and environmental stress and contributes to inflammatory responses in the lung that result in airway disease. Regulation by microRNAs (miRNAs) has emerged as an important post-transcriptional mechanism regulating gene expression that may modulate ASM phenotype but little is known about the expression and functions of miRNA in smooth muscle. In the present studies, we use microarrays to determine if miRNAs in human ASM cells are altered by a pro-inflammatory stimulus. In ASM cells exposed to IL-1beta, TNFalpha, and IFNgamma, we found 11 miRNA signi... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2549131 Wed, 17 Jun 2009 23:00:00 +0100 2549131 http://www.medworm.com/index.php?rid=2549130&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%3D19541843%26dopt%3DAbstract Authors: Wells SM, Buford MC, Porter VM, Brunell HL, Bunderson-Schelvan M, Nevin AB, Cardozo-Pelaez F, Holian A Although use of methamphetamine (MA) by smoking is the fastest growing method of administration, very limited data are available describing the effects of smoked MA. Using a murine inhalation exposure system, we explored the pulmonary effects of low-dose acute inhalation exposure to MA vapor (smoke). Inhalation of MA vapor resulted in transiently reduced pulmonary function as measured by transpulmonary resistance (RL), dynamic compliance (Cdyn), and whole body plethysmography (WBP) compared to unexposed controls. These changes were associated with an approximately 34% reduction in serotonin (5-HT) metabolism to 5-hydroxyindolacetic acid (5-HIAA) and a nearly 40% reduction in ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2549130 Wed, 17 Jun 2009 23:00:00 +0100 2549130 http://www.medworm.com/index.php?rid=2549129&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%3D19541844%26dopt%3DAbstract Authors: Wu S, Platteau A, Chen S, McNamara G, Whitsett J, Bancalari E Connective tissue growth factor (CTGF) is a member of an emerging family of immediate-early gene products that coordinates complex biological processes during development, differentiation and tissue repair. Over-expression of CTGF is associated with mechanical ventilation with high tidal volume and oxygen exposure in newborn lungs. However, the role of CTGF in postnatal lung development and remodeling is not well understood. In the present study, a double transgenic mouse model was generated with doxycycline-inducible over-expression of CTGF in respiratory epithelial cells. Over-expression of CTGF from postnatal day 1 to 14 resulted in thicker alveolar septa and decreased secondary septal formation. This is correlat... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2549129 Wed, 17 Jun 2009 23:00:00 +0100 2549129 http://www.medworm.com/index.php?rid=2549141&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%3D19520914%26dopt%3DAbstract Authors: Curran DR, Cohn L Mucous cell metaplasia is induced in response to harmful insults and provides front-line protection to clear the airway of toxic substances and cellular debris. In chronic airway diseases mucous metaplasia persists and results in airway obstruction and contributes significantly to morbidity and mortality. Mucus hypersecretion involves increased expression of mucin genes, and increased mucin production and release. The past decade has seen significant advances in our understanding of the molecular mechanisms by which these events occur. Inflammation stimulates EGFR activation and IL-13 to induce both Clara and ciliated cells to transition into goblet cells through the coordinated actions of FoxA2, TTF-1, SPDEF, GABAAR. Ultimately, these steps lead to upregulat... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2549141 Wed, 10 Jun 2009 23:00:00 +0100 2549141 http://www.medworm.com/index.php?rid=2549140&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%3D19520915%26dopt%3DAbstract In conclusion, activating Nrf2 pathways in tissue-specific Keap1 knockout mice represents an important genetic approach against oxidant induced lung damage. PMID: 19520915 [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=2549140 Wed, 10 Jun 2009 23:00:00 +0100 2549140 http://www.medworm.com/index.php?rid=2549139&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%3D19520916%26dopt%3DAbstract Authors: Bangel-Ruland N, Sobczak K, Christmann T, Kentrup D, Langhorst H, Kusche-Vihrog K, Weber WM The epithelial sodium channel (ENaC) mediates the first step in Na(+) reabsorption in epithelia cells such as kidney, colon, and airways and may consist of four homologous subunits (alpha, beta, gamma, delta). Predominantly, the alpha-subunit is expressed in these epithelia and it usually forms functional channels with the beta- and gamma-subunits. The delta-subunit was first found in human brain and kidney but the expression was also detected in human cell lines of lung, pancreatic and colonic origin. When co-expressed with beta and gamma accessory subunits in heterologous systems the two known isoforms of the delta-ENaC subunit (delta1 and delta2) can build amiloride-sensitive Na(+) c... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2549139 Wed, 10 Jun 2009 23:00:00 +0100 2549139 http://www.medworm.com/index.php?rid=2549138&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%3D19520917%26dopt%3DAbstract Authors: Lu Y, Azad N, Wang L, Iyer AK, Castranova V, Jiang BH, Rojanasakul Y Abnormal repair and dysregulated angiogenesis have been implicated in the pathogenesis of pulmonary fibrosis but the underlying mechanisms of regulation are not well understood. The present study investigated the role of phosphatidylinositol-3-kinase (PI3K)/Akt in fibrogenesis of human lung fibroblasts and its regulation by reactive oxygen species (ROS). Exposure of lung fibroblasts to bleomycin, a known inducer of fibrosis, resulted in rapid activation of PI3K/Akt and a parallel increase in fibroblast proliferation and collagen production, characteristics of lung fibrosis. Bleomycin had no significant effect on total Akt protein expression but induced phosphorylation of the protein at threonine 308 and serin... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2549138 Wed, 10 Jun 2009 23:00:00 +0100 2549138 http://www.medworm.com/index.php?rid=2549137&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%3D19520918%26dopt%3DAbstract The objective of this investigation was to determine the role of Pyk2, an intracellular non-receptor protein tyrosine kinase for post-adhesive inflammatory cell migration, on airway inflammation and hyperresponsiveness in immune sensitized mice. Blockade of Pyk2 was effected by intraperitonial administration of dominant negative C-terminal Pyk2 fused to a TAT protein transduction domain (TAT-Pyk2-CT). Ovalbumin challenge elicited infiltration of both eosinophils and lymphocytes into airways, increased mucus-containing epithelial cells, and caused increased airway hyperresponsiveness to methacholine in immune-sensitized mice. Pretreatment with 10 mg/kg TAT-Pyk2-CT i.p. blocked all of these effects and further decreased secretion of Th2 cytokine IL-4, IL-5 and IL-13 into the BAL fluid. Intra... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2549137 Wed, 10 Jun 2009 23:00:00 +0100 2549137 http://www.medworm.com/index.php?rid=2549136&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%3D19520919%26dopt%3DAbstract CONCLUSIONS: These results demonstrate that PM induces ROS generation in human lung endothelium resulting in oxidative stress-mediated EC barrier disruption via p38 MAP kinase- and HSP27-dependent pathways. These findings support a novel mechanism for PM-induced lung dysfunction and adverse cardiopulmonary outcomes. Funded by EPA/Johns Hopkins PM Center RD832417-010. PMID: 19520919 [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=2549136 Wed, 10 Jun 2009 23:00:00 +0100 2549136 http://www.medworm.com/index.php?rid=2549135&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%3D19520920%26dopt%3DAbstract Authors: Plant PJ, Brooks D, Faughnan M, Bayley T, Bain J, Singer L, Correa J, Pearce D, Binnie M, Batt J Skeletal muscle atrophy in individuals with advanced COPD is associated with diminished quality of life, increased health resource utilization and worsened survival. Muscle wasting results from an imbalance between protein degradation and synthesis and is enhanced by decreased regenerative repair. We investigated the activation of cellular signalling networks known to mediate muscle atrophy and regulate muscle regenerative capacity in rodent models, in individuals with COPD (FEV1 < 50% predicted). Nine COPD patients and nine control individuals were studied. Quadriceps femoris muscle isometric contractile force and cross-sectional area were confirmed to be significantly smaller ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2549135 Wed, 10 Jun 2009 23:00:00 +0100 2549135 http://www.medworm.com/index.php?rid=2549134&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%3D19520921%26dopt%3DAbstract Authors: Nisbet RE, Bland JM, Kleinhenz DJ, Mitchell PO, Walp ER, Sutliff RL, Hart CM Chronic hypoxia contributes to pulmonary hypertension through complex mechanisms that include enhanced NADPH oxidase expression and reactive oxygen species generation in the lung. Stimulation of peroxisome proliferator-activated receptor gamma (PPARgamma) reduces the expression and activity of NADPH oxidase. Therefore, we hypothesized that activating PPARgamma with rosiglitazone would attenuate chronic hypoxia-induced pulmonary hypertension, in part, through suppressing NADPH oxidase-derived ROS that stimulate proliferative signaling pathways. Male C57Bl/6 mice were exposed to chronic hypoxia (CH, FiO2 10%) or room air for 3 or 5 weeks. During the last 10 days of exposure, each animal was treated dail... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2549134 Wed, 10 Jun 2009 23:00:00 +0100 2549134 http://www.medworm.com/index.php?rid=2549133&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%3D19520922%26dopt%3DAbstract Authors: Pittet LA, Hall-Stoodley L, Rutkowski MR, Harmsen AG Influenza virus infections increase susceptibility to secondary bacterial infections, such as pneumococcal pneumonia, resulting in increased morbidity and mortality. Influenza-induced tissue damage is hypothesized to increase susceptibility to Streptococcus pneumoniae infection by increasing adherence to the respiratory epithelium. Using a mouse model of influenza infection followed by S. pneumoniae infection, we found that an influenza infection does not increase the number of pneumococci initially present within the trachea but does inhibit pneumococcal clearance by 2 hours post-infection. To determine whether influenza damage increases pneumococcal adherence, we developed a novel murine tracheal explant system to determin... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2549133 Wed, 10 Jun 2009 23:00:00 +0100 2549133 http://www.medworm.com/index.php?rid=2472041&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%3D19502384%26dopt%3DAbstract Authors: Jurkuvenaite A, Chen L, Bartoszewski R, Goldstein R, Bebok Z, Matalon S, Collawn JF The most common mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, DeltaF508, results in the production of a misfolded protein that is rapidly degraded. The mutant protein is temperature sensitive, and prior studies indicate that the low temperature-rescued channel is poorly responsive to physiological stimuli and is rapidly degraded from the cell surface at 37 degrees C. In the present studies, we tested the effect of a recently characterized pharmacological corrector, corr-4a, on cell surface stability and function of the low-temperature rescued DeltaF508 CFTR. We demonstrated that corr-4a significantly enhanced the protein stability of rescued DeltaF508 CFTR for... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472041 Fri, 05 Jun 2009 04:00:00 +0100 2472041 http://www.medworm.com/index.php?rid=2472039&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%3D19502385%26dopt%3DAbstract Authors: Parti RP, Loper R, Brown GD, Gordon S, Taylor PR, Bonventre JV, Murphy RC, Williams DL, Leslie CC Candida albicans is an increasingly important pulmonary fungal pathogen. Resident alveolar macrophages are important in host defense against opportunistic fungal infections. Activation of Group 1VA cytosolic phospholipase A2alpha (cPLA2alpha) in macrophages initiates arachidonic acid (AA) release for production of eicosanoids, which regulate inflammation and immune responses. We investigated the ability of C. albicans to activate cPLA2alpha in unprimed alveolar macrophages and after priming with GM-CSF, which regulates alveolar macrophage maturation. AA was released within minutes by GM-CSF-primed but not unprimed alveolar macrophages in response to C. albicans, and was blocked by... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472039 Fri, 05 Jun 2009 04:00:00 +0100 2472039 http://www.medworm.com/index.php?rid=2472036&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%3D19502386%26dopt%3DAbstract Authors: Busacca S, Germano S, De Cecco L, Rinaldi M, Comoglio F, Favero F, Murer B, Mutti L, Pierotti M, Gaudino G MicroRNAs (miRNAs) post-transcriptionally regulate the expression of target genes and may behave as oncogenes or tumor suppressors. Human malignant mesothelioma is an asbestos-related cancer, with poor prognosis and low median survival. Here we report for the first time a cross-evaluation of miRNA expression in mesothelioma (MPP-89, REN) and mesothelial cells (HMC-TERT). Microarray profiling, confirmed by Real Time quantitative RT-PCR (qRT-PCR), revealed a differential expression of miRNAs between mesothelioma and mesothelial cells. In addition, a computational analysis combining miRNA and gene expression profiles allowed the accurate prediction of genes potentially targe... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472036 Fri, 05 Jun 2009 04:00:00 +0100 2472036 http://www.medworm.com/index.php?rid=2472033&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%3D19502387%26dopt%3DAbstract Authors: John G, Yildirim AO, Rubin BK, Gruenert DC, Henke MO Airway epithelial cells contribute to the inflammatory response of the lung and their innate immune response is primarily mediated via Toll-like receptor (TLR) signaling. Cystic fibrosis (CF) airways are chronically infected with Pseudomonas aeruginosa, suggesting a modified immune response in CF. We investigated the TLR-4 expression and the inflammatory profile (Interleukin (IL)-8 and IL-6 secretion) in CF bronchial epithelial cell line CFBE41o- and its CFTR corrected counterpart grown under air-liquid interface conditions after stimulation with lipopolysaccharide (LPS) from Gram-negative bacteria. In CFTR corrected cells, IL-8 and IL-6 secretions were constitutively activated but significantly increased after LPS stimulati... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472033 Fri, 05 Jun 2009 04:00:00 +0100 2472033 http://www.medworm.com/index.php?rid=2472030&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%3D19502388%26dopt%3DAbstract Authors: Delmotte P, Sanderson MJ Formoterol, a long-acting ss2-receptor agonist, is used to relieve bronchial constriction. However, formoterol is often a racemic formulation and contains both (R,R)- and (S,S)-enantiomers. Because the activity of each isomer is poorly defined, the mechanisms by which formoterol relaxes smooth muscle cells (SMC) of intrapulmonary airways are not well understood. Consequently, we compared the effects of (S,S)-, (R,R)- and racemic formoterol, as well as (R)-albuterol, on the contraction and Ca(2+) signaling of airway SMCs in mouse lung slices with phase-contrast and confocal microscopy. Small airways were contracted with MCh and the associated SMCs displayed sustained Ca(2+) oscillations and an increase in Ca(2+) sensitivity. These contracted airways dis... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472030 Fri, 05 Jun 2009 04:00:00 +0100 2472030 http://www.medworm.com/index.php?rid=2472027&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%3D19502389%26dopt%3DAbstract The objective of this study was to characterize the impact of cigarette smoke exposure on lung immune and inflammatory processes. BALB/c and C57BL/6 mice were exposed to cigarette smoke for 4 days (acute) or >/=5 weeks (prolonged). Both mouse strains manifested an inflammatory response after acute smoke exposure, characterized by an influx of neutrophils, and mononuclear cells. Multiplex analysis revealed a greater than two fold increase of the cytokines IL-1alpha, IL-5, IL-6, and IL-18, as well as the chemokines MCP-1 and 3, MIP-1alpha, beta, and gamma, MIP-2, MIP-3beta, MDC, GCP-2, and IP-10. In BALB/c mice, neutrophilia persisted following prolonged exposure, while C57BL/6 showed evidence of attenuated neutrophilia both in the BAL and the lungs. In both mouse strains, cigarette smoke... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472027 Fri, 05 Jun 2009 04:00:00 +0100 2472027 http://www.medworm.com/index.php?rid=2472023&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%3D19502390%26dopt%3DAbstract Authors: Senft AP, Taylor RH, Lei W, Campbell SA, Tipper JL, Martinez MJ, Witt TL, Clay CC, Harrod KS Macrophages are the primary lung phagocyte and are instrumental in maintenance of a sterile, non-inflamed microenvironment. IFNs are produced in response to bacterial and viral infection and activate the macrophage to efficiently counteract and remove pathogenic invaders. Respiratory syncytial virus (RSV) inhibits IFN-mediated signaling mechanisms in epithelial cells; however, the effects on IFN signaling in the macrophage are currently unknown. We investigated the effect RSV infection had on IFN-mediated signaling in macrophages. RSV infection inhibited IFNbeta- and IFNgamma-activated transcriptional mechanisms in primary alveolar macrophages and macrophage cell lines, including the t... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472023 Fri, 05 Jun 2009 04:00:00 +0100 2472023 http://www.medworm.com/index.php?rid=2472052&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%3D19491339%26dopt%3DAbstract In this report we present evidence of a phosphoinositide-specific phospholipase C (PI-PLC) activity in Bronchoalveolar Lavage (BAL) fluid which may regulate PtdIns levels. Characterization of this extracellular activity showed specificity for PtdIns and phosphatidylinositol 4,5-bisphosphate, sharing the typical substrate concentration-, pH- and calcium-dependencies with mammalian PI-PLCs. Fractionation of BAL fluid showed that PI-PLC did not co-fractionate with large surfactant aggregates, but it was found mainly in the soluble fraction. Importantly, analysis of BAL samples from control and ARDS patients showed that the PI-PLC specific activity was decreased by 4-fold in ARDS samples concurrently with the increase in BAL PtdIns levels. Thus, we have identified for the first time an extrace... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472052 Tue, 02 Jun 2009 04:00:00 +0100 2472052 http://www.medworm.com/index.php?rid=2472048&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%3D19491340%26dopt%3DAbstract In this study, we tested the hypothesis that aging increases the susceptibility to CS-induced pulmonary inflammation using a mouse model. We subjected 9-week-old and 69-week-old C57BL/6J mice to CS (whole body exposure, 90 min/day), and evaluated neutrophil infiltration in the lungs, the levels of keratinocyte-derived chemokine (KC) and macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage (BAL) fluid, and mRNA expression in bronchiolar epithelium retrieved by laser capture microdissection. The 69-week-old mice showed a greater number of neutrophils and higher levels of bronchiolar KC and MIP-2 expression than 9-week-old mice after 9 days of CS exposure. Furthermore, single CS exposure induced the rapid upregulation of KC and MIP-2 in bronchiolar epithelium in both 9-week-old... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472048 Tue, 02 Jun 2009 04:00:00 +0100 2472048 http://www.medworm.com/index.php?rid=2472044&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%3D19491341%26dopt%3DAbstract Authors: Agapov E, Battaile JT, Tidwell R, Hachem R, Patterson GA, Pierce RA, Atkinson JJ, Holtzman MJ Diagnosis and therapy of chronic inflammatory lung disease is limited by the need for individualized biomarkers that provide insight into pathogenesis. Herein we show that mouse models of chronic obstructive lung disease exhibit an increase in lung chitinase production but cannot predict which chitinase family member may be equivalently increased in humans with corresponding lung disease. Moreover, we demonstrate that lung macrophage production of chitinase 1 is selectively increased in a subset of subjects with severe chronic obstructive pulmonary disease (COPD), and this increase is reflected in plasma levels. The findings provide a means to noninvasively track alternatively activat... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472044 Tue, 02 Jun 2009 04:00:00 +0100 2472044 http://www.medworm.com/index.php?rid=2472179&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%3D19448151%26dopt%3DAbstract Authors: Kobzik L You and I make a good match, dear reader. Youâre hungry for knowledge (you are reading the Red Journal after all). Youâd love a trenchant review that is interesting to read, but youâll settle for an update that gets to the point. I will settle for being merely useful, but would love to be âa good readâ or at least droll. Our goal is to survey how--or whether--basic advances in nitric oxide biology have been translated into the clinic. Letâs face the bad news right at the beginning. There has been breathtaking progress in NO biology at the molecular, cell and tissue level, but this has not--yet-- translated into a bonanza of new drugs or diagnostics. Donât give up just because I have leaked the punch line! There is much to learn (and ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472179 Fri, 15 May 2009 04:00:00 +0100 2472179 http://www.medworm.com/index.php?rid=2472150&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%3D19448152%26dopt%3DAbstract Conclusions: We have demonstrated that a reduction in endogenous N/OFQ or the lack of its receptor causes an increase in capsaicin induced bronchoconstriction implying a role for the N/OFQ-NOP receptor system in the modulation of capsaicin effects. Moreover, for the first time we documented differential airway responsiveness to capsaicin between naive and sensitized mice due, at least in part, to decreased endogenous N/OFQ levels in sensitized mice. PMID: 19448152 [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=2472150 Fri, 15 May 2009 04:00:00 +0100 2472150 http://www.medworm.com/index.php?rid=2472131&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%3D19448153%26dopt%3DAbstract In this study, we examined the effect of chronic acetylcholine (ACh) exposure at different muscle lengths to gain insights into the consequence of increased tone on the mechanical properties of ASM. The total force (the ACh-induced tone plus active force induced by a second stimulus - electric field stimulation (EFS)) increased immediately after induction of muscle tone, and increased further over time in the presence of the tone in a process termed âforce adaptationâ. The phenomenon of force adaptation was observed over a wide range of muscle lengths and did not prevent length adaptation when the muscle was adapted to the tone prior to being subjected to a length change, suggesting that both length and force adaptations can occur sequentially and in an independent fashion in the... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472131 Fri, 15 May 2009 04:00:00 +0100 2472131 http://www.medworm.com/index.php?rid=2472123&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%3D19448154%26dopt%3DAbstract Authors: Cho KJ, Seo JM, Shin Y, Yoo MH, Park CS, Lee SH, Chang YS, Cho SH, Kim JH BLT2 is a low-affinity receptor for leukotriene B4, a potent lipid mediator of inflammation generated from arachidonic acid via the 5-lipoxygenase (5-LO) pathway. Unlike BLT1, a high-affinity receptor for leukotriene B4, no clear physiological function has yet been identified for BLT2, especially with regard to the pathogenesis of asthma. The aim of this study was to investigate whether BLT2 plays a role in the pathogenesis of asthma. A murine model of allergic asthma was used to evaluate the role of BLT2 in ovalbumin-induced airway inflammation and airway hyperresponsiveness. The levels of BLT2 mRNA and its ligand, leukotriene B4, in the lung airway were highly elevated after OVA challenge, and downregu... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472123 Fri, 15 May 2009 04:00:00 +0100 2472123 http://www.medworm.com/index.php?rid=2472067&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%3D19448155%26dopt%3DAbstract In this study, we investigated the effect of Flt3-L in a clinically relevant aeroallergen-induced asthma on the phenotypic expression of lung T-cells. Balb/c mice were sensitized and challenged with cockroach (CRA) and AHR to methacholine was established. These mice received three i.p. injections of anti CD25 antibody (PC61) (250 microg) and Flt3-L (3microg) daily for ten days. Cytokines and immunoglobulins levels in the serum were measured and differential BALF cell counts were examined. Flt3-L reversed AHR to methacholine to the control level. Flt3-L significantly decreased levels of BALF IL-5, IFN-gamma, eosinophilia and substantially increased IL-10 and the number of CD4(+)CD25(+)Foxp3(+)IL-10(+) T-cells in the lung. Administration of PC61 antibody blocked the effect of Flt3-L and subs... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472067 Fri, 15 May 2009 04:00:00 +0100 2472067 http://www.medworm.com/index.php?rid=2472063&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%3D19448156%26dopt%3DAbstract Authors: Hoogerwerf JJ, de Vos AF, Van't Veer C, Bresser P, de Boer A, Tanck MW, Draing C, van der Zee JS, van der Poll T The airways are continuously exposed to respiratory pathogens, which may result in bacterial pneumonia, one of the most common infectious diseases and the leading cause of sepsis. Considering that recurrent exposure to microbial products can lead to tolerance of immune cells and that this might contribute to the susceptibility to nosocomial infection, we investigated the effect of in vivo lipopolysaccharide (LPS) instillation on the responsiveness of alveolar macrophages. In eight healthy humans sterile saline was instilled into a lung segment by bronchoscope, followed by instillation of LPS into the contralateral lung; 6h later a bilateral bronchoalveolar lavage wa... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472063 Fri, 15 May 2009 04:00:00 +0100 2472063 http://www.medworm.com/index.php?rid=2472059&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%3D19448157%26dopt%3DAbstract Authors: Phin S, Marchand-Adam S, Fabre A, Marchal-Somme J, Bantsimba-Malanda C, Kataoka H, Soler P, Crestani B Hepatocyte growth factor (HGF) is a growth factor for alveolar epithelial cells. Activation of Pro-HGF to HGF is regulated by the HGF activator (HGFA), a serine protease, and a specific inhibitor (HGFA inhibitor-1, HAI-1). An imbalance in the HGFA/HAI-1 system might contribute to lung fibrosis. ProHGF activation capacity from BAL fluid was evaluated 3, 7 and 14 days after the intratracheal bleomycin injection (Bleo) in mice with or without thrombin. BAL fluid from naive mice was used as control. HGFA and HAI-1 mRNA were evaluated by QPCR in the whole lung or by Western Blot in BAL fluid. BAL fluid from control mice and Bleo mice activated proHGF in vitro at a similar degree. ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472059 Fri, 15 May 2009 04:00:00 +0100 2472059 http://www.medworm.com/index.php?rid=2472055&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%3D19448158%26dopt%3DAbstract This study also yielded a novel experimental model that should prove particularly useful for further studies of CDH. PMID: 19448158 [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=2472055 Fri, 15 May 2009 04:00:00 +0100 2472055 http://www.medworm.com/index.php?rid=2472317&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%3D19423770%26dopt%3DAbstract Authors: Noah JW, Noah DL, Matalon S N/A. PMID: 19423770 [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=2472317 Thu, 07 May 2009 04:00:00 +0100 2472317 http://www.medworm.com/index.php?rid=2472286&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%3D19423771%26dopt%3DAbstract Authors: Conkright JJ, Apsley KS, Martin EP, Ridsdale R, Rice WR, Na CL, Yang B, Weaver TE We previously proposed a model of surfactant protein C (SP-C) biosynthesis in which internalization of the proprotein from the limiting membrane of the multivesicular body to internal vesicles represents a key step in the processing and secretion of SP-C. In order to test this hypothesis alanine mutagenesis of the N-terminal propeptide of SP-C was performed. Adenoviruses encoding mutant proproteins were infected into type II cells isolated from Sftpc-/- mice and medias analyzed for secreted SP-C 24h post-infection. Mutation of S12PPDYS17 completely blocked secretion of SP-C. PPDY (PY motif) has previously been shown to bind WW domains of Nedd4-like, E3 ubiquitin ligases. Purified recombinant GST-... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472286 Thu, 07 May 2009 04:00:00 +0100 2472286 http://www.medworm.com/index.php?rid=2472270&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%3D19423772%26dopt%3DAbstract Authors: Hewitt M, Estell K, Davis IC, Schwiebert LM We have reported that moderate intensity aerobic exercise training attenuates airway inflammation in mice sensitized/challenged with ovalbumin (OVA). The current study determined the effects of repeated bouts of aerobic exercise at a moderate intensity on airway hyperresponsiveness (AHR) in these mice. Mice were sensitized/challenged with OVA or saline and exercised at a moderate intensity 3X / wk for 4 wks. At protocol completion, mice were analyzed for changes in AHR via mechanical ventilation. Results show that exercise decreased total lung resistance 60% in OVA-treated mice as compared with controls; exercise also decreased airway smooth muscle (ASM) thickness. In contrast, exercise increased circulating epinephrine levels 3-fold... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472270 Thu, 07 May 2009 04:00:00 +0100 2472270 http://www.medworm.com/index.php?rid=2472227&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%3D19423773%26dopt%3DAbstract Authors: Snyder JC, Reynolds SD, Hollingsworth JW, Li Z, Kaminski N, Stripp BR Chronic lung diseases are marked by excessive inflammation and epithelial remodeling. Reduced Clara cell secretory function and corresponding decreases in the abundance of the major Clara cell secreted protein, CCSP, are characteristically seen in these disease states. We sought to define the impact of Clara cell and CCSP depletion on regulation of the lung inflammatory response. We used chemical and genetic mouse models of Clara cell and CCSP deficiency (CCSP-/-) coupled with P. aeruginosa lipopolysaccharide (LPS) elicited inflammation. Exposure of Clara cell depleted or CCSP-/- mice to LPS resulted in augmented inflammation as assessed by polymorphonuclear leukocyte recruitment to the airspace. Gene expres... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472227 Thu, 07 May 2009 04:00:00 +0100 2472227 http://www.medworm.com/index.php?rid=2472194&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%3D19423774%26dopt%3DAbstract Authors: Koval M, Ward C, Findley MK, Roser-Page S, Helms MN, Roman J The lung is dynamically remodeled in response to injury which alters extracellular matrix composition and can lead to either healthy or impaired lung regeneration. To determine how changes in extracellular matrix can influence alveolar epithelial barrier function, we examined the expression and function of tight junction proteins by rat alveolar epithelial type II cells cultured on one of three different matrix components: type I collagen or fibronectin, matrix glycoproteins which are highly expressed in injured lungs or laminin, a basement membrane matrix component. Of note, alveolar epithelial cells cultured for 2 days on fibronectin formed high resistance barriers and showed continuous claudin-3 and claudin-18 loc... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472194 Thu, 07 May 2009 04:00:00 +0100 2472194 http://www.medworm.com/index.php?rid=2472373&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%3D19411612%26dopt%3DAbstract Authors: Hodge S, Matthews G, Dean MM, Ahern J, Djukic M, Hodge G, Jersmann H, Holmes M, Reynolds PN Defective efferocytosis in the airway may perpetuate inflammation in smokers with/without COPD. Mannose binding lectin (MBL) improves efferocytosis in vitro; however, the effects of in vivo administration are unknown. MBL circulates in complex with MBL-associated serine proteases (MASPs), and efferocytosis involves activation of cytoskeletal-remodeling molecules including Rac1/2/3. We hypothesized that MBL would improve efferocytosis in vivo and that possible mechanisms for this effect would include upregulation of Rac1/2/3 or MASPs. We utilized a smoking mouse model to investigate the effects of MBL on efferocytosis. MBL (20microg/20g mouse) was administered via nebulizer to smoke-expo... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472373 Fri, 01 May 2009 04:00:00 +0100 2472373 http://www.medworm.com/index.php?rid=2472350&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%3D19411613%26dopt%3DAbstract Authors: Bäckström E, Lappalainen U, Bry K Little is known about the influence of maternal inflammation on neonatal outcome. Production of IL-1beta in the lungs of newborn infants is associated with bronchopulmonary dysplasia (BPD). Using bitransgenic mice in which human (h)IL-1beta is expressed with a doxycycline-inducible system controlled by the Clara cell secretory protein (CCSP) promoter, we have shown that hIL-1beta expression causes a BPD-like illness in infant mice. To study the hypothesis that maternal hIL-1beta production modifies the response of the newborn to hIL-1beta, doxycycline was administered to bitransgenic and control dams from embryonic day (E) 0, inducing production of hIL-1beta by the bitransgenic dams before hIL-1beta production started in their bitran... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472350 Fri, 01 May 2009 04:00:00 +0100 2472350 http://www.medworm.com/index.php?rid=2472450&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%3D19395678%26dopt%3DAbstract Conclusions: We conclude that TSC1/TSC2 deficiency leads to MMP-2 overproduction that is rapamycin insensitive, and that several genes exhibit similar patterns suggesting TSC1/TSC2 dependent but mTOR independent pathways may be involved in the pathogenesis of LAM. PMID: 19395678 [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=2472450 Fri, 24 Apr 2009 04:00:00 +0100 2472450 http://www.medworm.com/index.php?rid=2472431&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%3D19395679%26dopt%3DAbstract Authors: Hu B, Wu YM, Wu Z, Phan SH Myofibroblasts are known to play key roles in wound healing and fibrosis. They are thought to arise de novo from fibroblasts and characterized by induction of alpha-smooth muscle actin (alpha-SMA) expression. The homeobox transcription factor Csx/Nkx2.5 is critical in heart development and cardiogenesis by inducing expression of genes associated with cardiomyocyte differentiation. Herewith we report a novel repressor activity of Nkx2.5 on myofibroblast differentiation. Since a key marker of myofibroblast differentiation is expression of the alpha-SMA gene, we first scanned its promoter region for possible cis-acting elements. The results showed three potential binding sites (designated as NKE1, 2 and 3) containing the Nkx2.5/Csx consensus binding mot... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472431 Fri, 24 Apr 2009 04:00:00 +0100 2472431 http://www.medworm.com/index.php?rid=2472402&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%3D19395680%26dopt%3DAbstract Authors: Irwin D, Buehler PW, Alayash AI, Jia Y, Bonventura J, Foreman B, White M, Jacobs R, Piteo B, Tissotvanpatot MC, Hamilton KL, Gotshall RW Hemoglobin based oxygen carriers (HBOCs) are being developed as a potential therapy for increasing tissue oxygenation, yet they have not yet reached their full potential because of unwanted hemodynamic side effects (vasoconstriction, low cardiac output and oxygen delivery) due to nitric oxide (NO) scavenging by cell-free hemoglobin. It may be possible to overcome the NO scavenging effect by co-infusing S-nitrosylated (SNO) HBOC along with unmodified HBOC. SNO-HBOC like free hemoglobin may act as an NO donor in low oxygen conditions. We hypothesized that during hypoxia an unaltered HBOC, polymerized bovine hemoglobin (PBvHb) co-infused with a ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472402 Fri, 24 Apr 2009 04:00:00 +0100 2472402 http://www.medworm.com/index.php?rid=2472608&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%3D19372243%26dopt%3DAbstract Authors: Zaba LC, Smith GP, Sanchez M, Prystowsky SD Sarcoidosis is a non-caseating granulomatous disease likely of autoimmune etiology, that causes inflammation and tissue damage in multiple organs, most commonly the lung, but also skin, and lymph nodes. Reduced dendritic cell (DC) function in sarcoidosis peripheral blood compared to controls suggests that blunted end organ cellular immunity may contribute to sarcoidosis pathogenesis. Successful treatment of sarcoidosis with tumor necrosis factor (TNF) inhibitors, which modulate DC maturation and migration, has also been reported. Taken together, these observations suggest that DCs may be important mediators of sarcoidosis immunology. This review focuses on the phenotype and function of DCs in the lung, skin, blood, and lymph node of ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472608 Thu, 16 Apr 2009 04:00:00 +0100 2472608 http://www.medworm.com/index.php?rid=2472590&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%3D19372244%26dopt%3DAbstract Conclusions. Our data indicates that IL-10-treated human dendritic cells induce Th2 cell allergen tolerance ex vivo by driving the differentiation of regulatory T cells. PMID: 19372244 [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=2472590 Thu, 16 Apr 2009 04:00:00 +0100 2472590 http://www.medworm.com/index.php?rid=2472552&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%3D19372245%26dopt%3DAbstract Authors: Heijink IH, Postma DS, Noordhoek JA, Broekema M, Kapus A The molecular basis of airway remodeling and loss of epithelial integrity in asthma is still undefined. We aimed to establish if exposure of human bronchial epithelium (16HBE cells) to asthma-related stimuli can induce epithelial-to-mesenchymal transition (EMT), a key process in tissue repair and remodeling associated with loss of intercellular contacts. We studied the effects of fibrogenic cytokine TGF-beta and protease-containing aeroallergen house dust mite (HDM) on mesenchymal and epithelial markers, cytoskeleton organization and activation of beta-catenin-driven reporter TopFLASH. TGF-beta alone upregulated vimentin and fibronectin, modestly downregulated E-cadherin, but did not affect cytokeratin. HDM alone did not... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472552 Thu, 16 Apr 2009 04:00:00 +0100 2472552 http://www.medworm.com/index.php?rid=2472532&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%3D19372246%26dopt%3DAbstract Authors: Cha SI, Groshong SD, Frankel SK, Edelman BL, Cosgrove GP, Terry-Powers JL, Remigio LK, Curran-Everett D, Brown KK, Cool CD, Riches DW Increased apoptosis of alveolar epithelial cells and impaired apoptosis of myofibroblasts have been linked to the pathogenesis of idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP). Fas, a death receptor of the TNF-receptor superfamily, has been implicated in apoptosis of both cell types, though the mechanisms are poorly understood. The goals of this study were: (i) to examine the localization of c-FLIP, an NF-kappaB-dependent regulator of Fas-signaling, in lung tissues from IPF/UIP patients and control subjects, and (ii) to compare c-FLIP expression with epithelial cell and myofibroblast apoptosis, proliferation and NF-kappaB ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472532 Thu, 16 Apr 2009 04:00:00 +0100 2472532 http://www.medworm.com/index.php?rid=2472513&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%3D19372247%26dopt%3DAbstract In this study we used an air-liquid interface model of human airway epithelia and measured TER, changes in TJ expression and architecture following exposure to live P. aeruginosa PAO1, and PAO1-Deltarhl which is a PAO1 mutant lacking rhlA and rhlB, which encode key enzymes for rhamnolipid production. In addition, the cells were challenged with bacterial culture medium conditioned by these strains, purified rhamnolipids or synthetic 3O-C12-HSL. Virulence factors secreted by P. aeruginosa reduced TER and caused TJ rearrangement in the bronchial epithelium, exposing the epithelium to further bacterial infiltration. Pretreatment of the bronchial epithelium with AZM attenuated this effect and facilitated epithelial recovery. These data suggest that AZM protects the bronchial epithelium during P... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472513 Thu, 16 Apr 2009 04:00:00 +0100 2472513 http://www.medworm.com/index.php?rid=2472493&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%3D19372248%26dopt%3DAbstract Authors: Wong PS, Vogel CF, Kokosinksi K, Matsumura F The arylhydrocarbon receptor (AhR) is known for its ability to bind aromatic containing compounds which starts a molecular cascade involving the induction of cytochrome P450s (cP450s) and inflammatory cytokines. Our hypothesis is that many inhaled environment toxicant components activate these inflammatory pathways via an initial binding to the AhR. To test this possibility, we treated Clara cell derived NCI-H441 cells with the AhR agonist TCDD and demonstrated that AhR activation increased the expression of both cP450s and inflammatory markers. We also found increased mucin 5AC production with TCDD treatment. Similar results were observed in NCI-H441 cells treated with urban dust particles (UDP). Mucin 5AC expression was highly cor... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472493 Thu, 16 Apr 2009 04:00:00 +0100 2472493 http://www.medworm.com/index.php?rid=2472473&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%3D19372249%26dopt%3DAbstract Authors: Roman J, Rangasamy T, Guo J, Sugunan S, Meednu N, Packirisamy G, Shimoda L, Golding A, Semenza G, Georas SN Secondary lymphoid organs and peripheral tissues are characterized by hypoxic microenvironments both in the steady state and during inflammation. Although hypoxia regulates T cell metabolism and survival, very little is known about whether or how hypoxia influences T cell activation. We stimulated mouse CD4+ T cells in vitro with antibodies directed against the T cell receptor (CD3) and CD28 under normoxic (20% 02) and hypoxic (1% 02) conditions. Here we report that stimulation under hypoxic conditions augments the secretion of effector CD4+ T cell cytokines, especially interferon gamma (IFN-gamma). The enhancing effects of hypoxia on IFN-gamma secretion were independent... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472473 Thu, 16 Apr 2009 04:00:00 +0100 2472473 http://www.medworm.com/index.php?rid=2472692&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%3D19346316%26dopt%3DAbstract Conclusion: Invasive pulmonary functions allow distinction between respiratory diseases in mice by clinically relevant variables and should become standard in the functional evaluation of pathological disease models. PMID: 19346316 [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=2472692 Fri, 03 Apr 2009 04:00:00 +0100 2472692 http://www.medworm.com/index.php?rid=2472672&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%3D19346317%26dopt%3DAbstract Authors: Bhattacharyya S, Solakyildirim K, Zhang Z, Chen ML, Linhardt RJ, Tobacman JK The chemokine Interleukin-8 (IL-8) is critically important in inflammatory processes in human tissues, and IL-8 interactions with sulfated glycosaminoglycans have been implicated in modification of inflammatory responses in bronchial epithelium. To determine the role of chondroitin-4-sulfate (C4S) in mediating effects of IL-8, we silenced the enzyme Arylsulfatase B (ASB; N-acetylgalactosamine-4-sulfatase) that removes the 4-sulfate group from chondroitin-4-sulfate (C4S) in the IB3-1 and C38 bronchial epithelial cell lines and in normal primary bronchial epithelial cells. When ASB was silenced and IL-8 production stimulated by exposure to TNF-alpha, ASB activity declined by ~75%, cellular C4S content i... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472672 Fri, 03 Apr 2009 04:00:00 +0100 2472672 http://www.medworm.com/index.php?rid=2472652&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%3D19346318%26dopt%3DAbstract Authors: Li MY, Hsin MK, Yip J, Mok TS, Underwood MJ, Chen GG Among the carcinogenic chemicals of cigarette smoking, NNK is the most potent. The activation of PPARgamma can arrest the growth of lung cancer. We hypothesized that PPARgamma activation inhibits NNK-mediated proliferation of lung cancer cells. PPARgamma expression was increased in 94.7% human lung cancer tumor tissues, compared to their paired corresponding non-tumor tissues. PPARgamma was also found abundant in all the lung cancer cell lines tested. Troglitazone dose-dependently inhibited the NNK inverted exclamation markVmediated proliferation of lung cancer cells that expressed PPARgamma. Troglitazone blocked NNK-induced up-regulation of HO-1, Bcl-2 and c-IAP2, and recovered Bad activity that was suppressed by NNK. NNK p... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472652 Fri, 03 Apr 2009 04:00:00 +0100 2472652 http://www.medworm.com/index.php?rid=2472631&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%3D19346319%26dopt%3DAbstract Conclusions: These data support further development of INO-4995 for the treatment of CF. PMID: 19346319 [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=2472631 Fri, 03 Apr 2009 04:00:00 +0100 2472631 http://www.medworm.com/index.php?rid=2472780&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%3D19329552%26dopt%3DAbstract This study investigated the effect of type I fCollagen on the phenotypic plasticity of human parenchymal fibroblasts (PFbs) in vitro. Cell numbers were 45% lower when cultured on fCollagen as compared to culture on its degradation product, monomeric collagen (mCollagen). DNA profiles indicated that fCollagen is anti-proliferative, rather than pro-apoptotic. fCollagen suppressed bFGF-stimulated increases in the levels of cyclin E and cdk2 mRNA. fCollagen also suppressed TGF-beta (100 pM)-stimulated increases in the mRNA and protein levels of alpha-smooth muscle actin (alpha-SMA), a marker of the myofibroblast phenotype. However, in cells exposed to fCollagen, the levels of metalloproteinases -1 and -14 (MMP-1 and MMP-14) mRNA, as well as active MMP-2 protein were increased by between 2 to 5... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472780 Fri, 27 Mar 2009 04:00:00 +0100 2472780 http://www.medworm.com/index.php?rid=2472765&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%3D19329553%26dopt%3DAbstract Conclusions: This sepsis model results in significant diaphragm calpain activation and calpain dependent diaphragm cytoskeletal protein cleavage. Moreover, calpain inhibition attenuates endotoxin induced diaphragm weakness suggesting that such inhibitors may be a potential treatment to improve respiratory muscle function in infected patients. PMID: 19329553 [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=2472765 Fri, 27 Mar 2009 04:00:00 +0100 2472765 http://www.medworm.com/index.php?rid=2472747&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%3D19329554%26dopt%3DAbstract Authors: Evans SE, Scott BL, Clement CG, Larson DT, Kontoyiannis D, Lewis RE, Lasala PR, Pawlik J, Peterson JW, Chopra AK, Klimpel G, Bowden G, Hook M, Xu Y, Tuvim MJ, Dickey BF Pneumonia is a serious problem worldwide. We recently demonstrated that innate defense mechanisms of the lung are highly inducible against pneumococcal pneumonia. To determine the breadth of protection conferred by stimulation of lung mucosal innate immunity, and to identify cells and signaling pathways activated by this treatment, mice were treated with an aerosolized bacterial lysate, then challenged with lethal doses of bacterial and fungal pathogens. Mice were highly protected against a broad array of Gram-positive, Gram-negative, and Class A bioterror bacterial pathogens, and the fungal pathogen Aspergillu... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472747 Fri, 27 Mar 2009 04:00:00 +0100 2472747 http://www.medworm.com/index.php?rid=2472728&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%3D19329555%26dopt%3DAbstract Authors: Königshoff M, Eickelberg O The WNT family of signaling proteins is essential to organ development in general and lung morphogenesis in particular. Originally identified as a developmentally active signaling pathway, the WNT pathway has recently been linked to the pathogenesis of important lung diseases, in particular lung cancer and pulmonary fibrosis. This review summarizes our current understanding about WNT signaling in lung development and disease and is structured into three chapters: The first chapter presents an introduction to WNT signaling, outlining WNT proteins, their receptors and signaling intermediates, as well as the regulation of this complex pathway. The second chapter focuses on the role of WNT signaling in the normal embryonic and adult lung, and highli... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472728 Fri, 27 Mar 2009 04:00:00 +0100 2472728 http://www.medworm.com/index.php?rid=2472710&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%3D19329556%26dopt%3DAbstract We report that DEP exposure induces increased levels of p21 mRNA and protein in a manner that is independent of p53 and Sp1 expression or DNA binding to the p21 gene. Using Chromatin Immuoprecipitation assays and expression of a dominant negative Stat3 mutant, we show that activation of Stat3 and its binding to the p21 promoter are required for DEP-induced expression of p21, suggesting that Stat3 plays an essential role in the induction of p21 by DEP. Additional experiments demonstrated that activation of p21 gene expression is dependent on the activation of EGFR and Src kinase activities. Lastly, we provide evidence suggesting that DEP exposure can inhibit the proliferation of human bronchial epithelial cells, suggesting a functional role of p21 activation airway epithelial cells exposed ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2472710 Fri, 27 Mar 2009 04:00:00 +0100 2472710 http://www.medworm.com/index.php?rid=2295541&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%3D19307610%26dopt%3DAbstract Authors: Suzuki T, Yamashita C, Zemans RL, Briones N, Van Linden A, Downey GP Leukocyte elastase induces apoptosis of lung epithelial cells via alterations in mitochondrial permeability but the signaling pathways regulating this response remain uncertain. Here we investigated the involvement of proteinase activated receptor-1 (PAR-1), the transcription factor NF-kappaB and the protooncogene p53 in this pathway. Elastase-induced apoptosis of human lung epithelial cells correlated temporally with activation of NF-kappaB, phosphorylation and nuclear translocation of p53, increased PUMA expression, and mitochondrial translocation of Bax resulting in enhanced permeability. Elastase-induced apoptosis was prevented by pharmacological inhibitors of NF-kappaB and p53 and by short interfering RN... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2295541 Mon, 23 Mar 2009 04:00:00 +0100 2295541 http://www.medworm.com/index.php?rid=2295536&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%3D19307611%26dopt%3DAbstract In this study, we examined whether PAR-1 contributes to inflammation and lung damage induced by fMLP, by comparing the response of PAR-1 deficient (PAR-1-/-) mice with that of wild-type (WT) mice. Mice were sacrificed at various time points after fMLP instillation (200microg/50microl). WT mice developed emphysema and goblet cell metaplasia (GCM). The onset of pulmonary lesions was preceded by an increase in thrombin immunoreactivity in bronchial airways and alveolar tissue. This was followed by a decrease in PAR-1 immunoreactivity, and by an increase in IL-13 immunostaining on the luminal surface of airway epithelial cells. In PAR-1-/- mice, fMLP administration induced similar responses in terms of inflammation and emphysema, but these mice were protected from the development of GCM. The i... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2295536 Mon, 23 Mar 2009 04:00:00 +0100 2295536 http://www.medworm.com/index.php?rid=2242044&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%3D19265173%26dopt%3DAbstract Authors: Theatre E, Bours V, Oury C Extracellular ATP, acting at P2Y and P2X receptors, has recently been shown to contribute to airway inflammation. The aim of our study was to investigate the molecular mechanisms involved in the ATP-dependent regulation of interleukin-8 production by airway epithelial cells. Treatment of the human tracheal NT-1 cells with ATP or its two analogs, alpha,beta-methyleneATP (alpha,beta-meATP) and 2'- and 3'-O-(4-benzoyl-benzoyl)-ATP (BzATP) activated NF-kappaB through the IkappaB kinase (IKK) complex, a process requiring Ca(2+), calmodulin (CaM) and Ca(2+)/CaM-dependent kinase (CaMK), but independent from phospholipase C (PLC). alpha,beta-meATP-induced IKK activation also occurred in the alveolar A549 cell line. Real-time RT-PCR revealed that NT-1 and A54... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2242044 Thu, 05 Mar 2009 05:00:00 +0100 2242044 http://www.medworm.com/index.php?rid=2242043&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%3D19265174%26dopt%3DAbstract Authors: Hoshino T, Okamoto M, Sakazaki Y, Kato S, Young HA, Aizawa H Administration of several chemotherapeutic drugs such as bleomycin, busulfan, and gefitinib often induces lethal lung injury. However, the precise mechanisms responsible for this drug-induced lung injury are still unclear. In the present study, we examined the role of the proinflammatory cytokines IL-18 and IL-1beta in the mechanism of bleomycin-induced lung injury. We performed immunohistochemical analysis of IL-18 and IL-18 receptoralpha (Ralpha) chain expression in the lungs of 5 patients with bleomycin-induced lethal lung injury. Enhanced expression of both IL-18 and IL-18Ralpha was observed in the lungs of all 5 patients with bleomycin-induced lung injury. To support the data obtained from patient samples, the l... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2242043 Thu, 05 Mar 2009 05:00:00 +0100 2242043 http://www.medworm.com/index.php?rid=2242042&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%3D19265175%26dopt%3DAbstract Authors: Tang D, Kang R, Xiao W, Zhang H, Lotze MT, Wang H, Xiao X The pathogenesis of sepsis is mediated in part by the pathogen associated molecular pattern molecule [PAMP], bacterial endotoxin, which stimulates macrophages to sequentially release early (e.g., TNF-alpha, IL-1beta) and late [e.g., high mobility group box 1 (HMGB1) protein] proinflammatory mediators. The recent discovery of HMGB1 as a late mediator of lethal sepsis has prompted investigation into development of several new experimental therapeutics either limiting release, blocking HMGB1 itself or its nominal receptors. Quercetin was recently identified as an experimental therapeutic that significantly protects against oxidative injury. Here, we report that quercetin attenuates lethal systemic inflammation caused by en... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2242042 Thu, 05 Mar 2009 05:00:00 +0100 2242042 http://www.medworm.com/index.php?rid=2174051&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%3D19202004%26dopt%3DAbstract Conclusions: These data suggest that mucosal vaccination with LPS-treated immunodominant CTL epitope-loaded DC is a promising strategy for generating protective CTL against respiratory infections with intracellular pathogens. PMID: 19202004 [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=2174051 Fri, 06 Feb 2009 05:00:00 +0100 2174051 http://www.medworm.com/index.php?rid=2174050&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%3D19202005%26dopt%3DAbstract Authors: Ikegami M, Weaver TE, Grant SN, Whitsett JA Alveolar capillaries are located in close proximity to the alveolar epithelium and beneath the surfactant film. We hypothesized that the shape of alveolar capillaries and accompanying oxygenation are influenced by surfactant surface tension in the alveolus. To prove our hypothesis, surfactant surface tension was regulated by conditional expression of surfactant protein (SP)-B in Sftpb(-/-) mice, thereby inhibiting surface tension lowering properties of surfactant in vivo within 24h after depletion of Sftpb. Minimum surface tension of isolated surfactant was increased and oxygen saturation was significantly reduced after 2d of SP-B deficiency in association with deformation of alveolar capillaries. Intravascularly injected 3.2microm d... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2174050 Fri, 06 Feb 2009 05:00:00 +0100 2174050 http://www.medworm.com/index.php?rid=2174049&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%3D19202006%26dopt%3DAbstract Authors: Chiba Y, Todoroki M, Nishida Y, Tanabe M, Misawa M Interleukin-13 (IL-13) is one of the central mediators for development of airway hyperresponsiveness in asthma. The signal transducer and activation of transcription 6 (STAT6) is one of the major signal transducers activated by IL-13, and a possible involvement of IL-13/STAT6 pathway in the augmented bronchial smooth muscle (BSM) contraction has been suggested. In the present study, the effect of a novel STAT6 inhibitor, AS1517499, on the development of antigen-induced BSM hyperresponsiveness was investigated. In cultured human BSM cells, IL-13 (100 ng/mL) caused a phosphorylation of STAT6 and an upregulation of RhoA, a monomeric GTPase responsible for Ca(2+) sensitization of smooth muscle contraction: both events were inhibit... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2174049 Fri, 06 Feb 2009 05:00:00 +0100 2174049 http://www.medworm.com/index.php?rid=2174048&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%3D19202007%26dopt%3DAbstract Authors: Maniatis NA, Harokopos V, Thanassopoulou A, Oikonomou N, Mersinias V, Witke W, Orfanos SE, Armaganidis A, Roussos C, Kotanidou A, Aidinis V Mechanical ventilation, an essential life-support modality of patients with Acute Lung Injury (ALI) or the Acute Respiratory Distress Syndrome (ARDS), exerts its detrimental effects through largely unknown mechanisms. Gelsolin (GSN), an actin binding protein and a substrate of caspace-3, was recently shown to play a major role in bleomycin- or lipopolysaccharide-induced lung injury. To dissect a possible role of GSN in the pathogenesis of Ventilator Induced Lung Injury (VILI), genetically modified mice lacking GSN expression and wild-type controls underwent mechanical ventilation with high tidal volumes. GSN was found upregulated in the ai... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2174048 Fri, 06 Feb 2009 05:00:00 +0100 2174048 http://www.medworm.com/index.php?rid=2161031&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%3D19188657%26dopt%3DAbstract Authors: Kramer EL, Mushaben EM, Pastura PA, Acciani TH, Deutsch GH, Khurana Hershey GK, Korfhagen TR, Hardie WD, Whitsett JA, Le Cras TD Transforming growth factor-alpha (TGF-alpha) and its receptor, the epidermal growth factor receptor (EGFR), are induced following lung injury and are associated with remodeling in chronic pulmonary diseases such as pulmonary fibrosis and asthma. Expression of TGF-alpha in the lungs of adult mice causes fibrosis, pleural thickening, and pulmonary hypertension (PH) in addition to increased expression of a transcription factor, early growth response-1 (Egr-1). Egr-1 was increased in airway smooth muscle (ASM) and the vascular adventitia in the lungs of mice conditionally expressing TGF-alpha in airway epithelium (CCSP-rtTA(+/-)/(tetO)7-TGF-alpha(+/-)). ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2161031 Mon, 02 Feb 2009 05:00:00 +0100 2161031 http://www.medworm.com/index.php?rid=2161030&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%3D19188658%26dopt%3DAbstract In this study we examined the role ET-1 in the regulation of lung fibroblast survival and apoptosis. ET-1 rapidly activates the pro-survival PI3K/AKT signaling pathway in normal and fibrotic human lung fibroblasts. ET-1-induced activation of PI3K/AKT is dependent on p38 MAPK but not ERK1/2, JNK or TGF-beta1. Activation of the PI3K/AKT pathway by ET-1 inhibits fibroblast apoptosis, and this inhibition is reversed by blockade of p38 MAPK or PI3K. Transforming growth factor beta-1 (TGF-beta1) has been shown to attenuate myofibroblast apoptosis through the p38 MAPK-dependent secretion of a soluble factor which activates PI3K/AKT. In this study, we show that although TGF-β1 induces fibroblast synthesis and secretion of ET-1, TGF-beta1 activation of PI3K/AKT is not dependent on ET-1. We... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2161030 Mon, 02 Feb 2009 05:00:00 +0100 2161030 http://www.medworm.com/index.php?rid=2161029&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%3D19188659%26dopt%3DAbstract Authors: Zhang R, Zhou L, Li Q, Liu J, Yao W, Wan H Hypoxia stimulates the migration of pulmonary artery smooth muscle cells (PASMCs), which contributes to the pathogenesis of pulmonary vessel structural remodeling in hypoxic pulmonary hypertension (HPH). In the present study, we found gelsolin-like actin-capping protein (CapG) and transgelin were preferentially expressed in hPAMSCs under hypoxia compared with normoxia using proteomics-based method. These two actin associated proteins, modulate a variety of physiological processes including motility of cells by interacting differently with the actin cytoskeleton. Our study showed that these two genes were upregulated at both mRNA and protein levels under hypoxia in hPASMCs. As a key transcriptional regulation factor under hypoxia, hypo... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2161029 Mon, 02 Feb 2009 05:00:00 +0100 2161029 http://www.medworm.com/index.php?rid=2161028&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%3D19188660%26dopt%3DAbstract Conclusion: This is the first time identifying the background K+ channel TASK-1 in the endothelin-1-mediated depolarization in native human PASMC and might represent a novel pathologic mechanism related to pulmonary arterial hypertension. PMID: 19188660 [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=2161028 Mon, 02 Feb 2009 05:00:00 +0100 2161028 http://www.medworm.com/index.php?rid=2161027&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%3D19188661%26dopt%3DAbstract Authors: Mouded M, Egea EE, Brown MJ, Hanlon SM, Houghton AM, Tsai LW, Ingenito EP, Shapiro SD Theories of emphysema traditionally revolved around proteolytic destruction of extracellular matrix. Models have recently been developed that show airspace enlargement with the induction of pulmonary cell apoptosis. The purpose of this study was to determine the mechanism by which a model of epithelial cell apoptosis caused airspace enlargement. Mice were treated with either intratracheal (IT) microcystin (MC) to induce apoptosis, IT porcine pancreatic elastase (PPE), or their respective vehicles. Mice from all groups were inflated and morphometry was measured at various time points. Physiology measurements were performed for airway resistance, tissue elastance, and lung volumes. The groups w... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2161027 Mon, 02 Feb 2009 05:00:00 +0100 2161027 http://www.medworm.com/index.php?rid=2116717&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%3D19151316%26dopt%3DAbstract Conclusions: Neonatal mice exposed to intranasal HDM developed eosinophilic inflammation, airway remodelling and AHR as reported in paediatric asthma. Importantly, all abnormalities developed in parallel, not sequentially, between 2 and 3 weeks of age. PMID: 19151316 [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=2116717 Fri, 16 Jan 2009 05:00:00 +0100 2116717 http://www.medworm.com/index.php?rid=2116716&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%3D19151317%26dopt%3DAbstract Authors: Malavia NK, Raub CB, Mahon SB, Brenner M, Panettieri Jr RA, George SC Communication between the airway epithelium and stroma is evident during embryogenesis, and both epithelial shedding and increased smooth muscle proliferation are features of airway remodeling. Hence, we hypothesized that following injury the airway epithelium could modulate airway smooth muscle proliferation. Fully differentiated primary normal human bronchial epithelial (NHBE) cells at an air-liquid interface were co-cultured with serum-deprived normal primary human airway smooth muscle cells (HASM) using commercially available Transwells(R). In some co-cultures, the NHBE were repeatedly (x4) scrape-injured. An in vivo model of tracheal injury consisted of gently denuding the tracheal epithelium (x3) of a ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2116716 Fri, 16 Jan 2009 05:00:00 +0100 2116716 http://www.medworm.com/index.php?rid=2116715&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%3D19151318%26dopt%3DAbstract Authors: Hosakote YM, Liu T, Castro SM, Garofalo RP, Casola A Oxidative stress plays an important role in the pathogenesis of lung inflammation. Respiratory syncytial virus (RSV) infection induces reactive oxygen species (ROS) production in vitro and oxidative injury in lungs in vivo, however, the mechanism of RSV-induced cellular oxidative stress has not been investigated. Therefore, we determined whether RSV infection of airway epithelial cells modified the expression and/or activities of antioxidant enzymes (AOE). A549 cells, a human alveolar type II-like epithelial cell line, and small airway epithelial (SAE) cells, normal human cells derived from terminal bronchioli, were infected with RSV and harvested at various time points to measure F2-8 isoprostanes, total and reduced glutath... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2116715 Fri, 16 Jan 2009 05:00:00 +0100 2116715 http://www.medworm.com/index.php?rid=2116714&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%3D19151319%26dopt%3DAbstract Authors: Kohan M, Breuer R, Berkman N Airway remodeling is a central feature of asthma; however, the mechanisms underlying its development have not been fully elucidated. We have demonstrated that osteopontin, an inflammatory cytokine and an extra-cellular matrix glycoprotein with profibrotic properties, is up-regulated in a murine model of allergen-induced airway remodeling. In the present study, we determined whether osteopontin plays a functional role in airway remodeling. Osteopontin deficient (-/-) and wild type mice were sensitized and exposed to inhaled ovalbumin or saline for 5 weeks. Collagen production, peribronchial smooth muscle area, mucus-producing cell number and bronchoalveolar cell counts were assessed. The functional behavior and phenotype of lung fibroblasts from ova... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2116714 Fri, 16 Jan 2009 05:00:00 +0100 2116714 http://www.medworm.com/index.php?rid=2116713&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%3D19151320%26dopt%3DAbstract Authors: Sandbo N, Kregel S, Taurin S, Bhorade S, Dulin NO Transforming growth factor-beta (TGF-beta) is a cytokine implicated in wound healing and in the pathogenesis of pulmonary fibrosis. TGF-beta stimulates myofibroblast differentiation characterized by expression of contractile smooth muscle (SM)-specific proteins such as SM-alpha-actin. In the present study, we examined the role of serum response factor (SRF) in the mechanism of TGF-beta-induced pulmonary myofibroblast differentiation of human lung fibroblasts (HLF). TGF-beta stimulated SM-alpha-actin expression in HLF which paralleled with a profound induction of SRF expression and activity. Inhibition of SRF by the pharmacologic SRF inhibitor (CCG-1423), or via adenovirus-mediated transduction of SRF short hairpin RNA (shSRF) b... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2116713 Fri, 16 Jan 2009 05:00:00 +0100 2116713 http://www.medworm.com/index.php?rid=2116712&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%3D19151321%26dopt%3DAbstract Authors: Koya T, Matsuda H, Matsubara S, Miyahara N, Dakhama A, Takeda K, Gelfand EW Dendritic cells (DCs) are considered to be the most efficient antigen presenting cells. Intratracheal administration of allergen-pulsed bone marrow-derived dendritic cells (BMDCs) prior to allergen challenge induces airway hyperresponsiveness (AHR) and inflammation. Ovalbumin (OVA)-pulsed BMDCs from wild-type (WT) mice were transferred into naive WT, CD4-/-, CD8-/-, or IL-13-/- mice. Two (short protocol) or 10 days (long protocol) after BMDC transfer, mice were challenged with 1% OVA for 3 days and assayed 2 days later. Transfer of OVA-primed BMDCs into BALB/c or C57BL/6 mice elicited AHR in both protocols. Airway eosinophilia, Th2 cytokines, or goblet cell metaplasia were only increased in the long bu... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2116712 Fri, 16 Jan 2009 05:00:00 +0100 2116712 http://www.medworm.com/index.php?rid=2116711&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%3D19151322%26dopt%3DAbstract This study tests the hypothesis that regulation of AA/phospholipid remodeling enzymes, cytosolic phospholipase A2 (cPLA2) and CoA-independent transacylase (CoA-IT), provides a mechanism for altered eosinophil survival during allergic asthma. In vitro incubation of human eosinophils (from non asthmatic donors) with IL-5 markedly increased cell survival, induced cPLA2 phosphorylation, and increased both cPLA2 and CoA-IT activity. Furthermore, treatment of eosinophils with non-selective (ET18-O-CH3) and selective (SK&F 98625) inhibitors of CoA-IT triggered apoptosis, measured by changes in morphology, membrane phosphatidylserine exposure, and caspase activation, completely reversing IL-5 induced eosinophil survival. To determine if similar activation occurs in vivo, human blood eosinophil... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=2116711 Fri, 16 Jan 2009 05:00:00 +0100 2116711 http://www.medworm.com/index.php?rid=2041199&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%3D19075182%26dopt%3DAbstract Authors: Perl AK, Zhang L, Whitsett JA PMID: 19075182 [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=2041199 Wed, 17 Dec 2008 15:06:51 +0100 2041199 http://www.medworm.com/index.php?rid=2041198&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%3D19075183%26dopt%3DAbstract Authors: Cutz E, Fu XW, Yeger H, Nurse CA PMID: 19075183 [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=2041198 Wed, 17 Dec 2008 15:06:46 +0100 2041198 http://www.medworm.com/index.php?rid=1943929&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%3D18988918%26dopt%3DAbstract Conclusions) These results suggest that activation of TLR3 can affect the differentiation to myofibroblasts and enhance ECM production via the NF-KB-TGF-beta1 dependent pathway. PMID: 18988918 [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=1943929 Thu, 06 Nov 2008 05:00:00 +0100 1943929 http://www.medworm.com/index.php?rid=1943928&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%3D18988919%26dopt%3DAbstract Conclusions In this mouse model, chronic cigarette smoke exposure resulted in systemic features that closely resemble the early signs of the extrapulmonary manifestations observed in COPD patients. PMID: 18988919 [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=1943928 Thu, 06 Nov 2008 05:00:00 +0100 1943928 http://www.medworm.com/index.php?rid=1943927&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%3D18988920%26dopt%3DAbstract Authors: Shukla MN, Rose JL, Ray R, Lathrop KL, Ray A, Ray P Idiopathic pulmonary fibrosis is a lethal parenchymal lung disease characterized by denudation of the lung epithelium, fibroblast proliferation and collagen deposition. Cellular changes underlying disease progression involve injury to alveolar epithelial cells, epithelial to mesenchymal transition, proliferation of alpha-smooth muscle actin-expressing myofibroblasts and of fibroblasts resulting in enhanced deposition of extracellular matrix proteins. Hepatocyte growth factor (HGF) inhibits progression of bleomycin-induced pulmonary fibrosis in mice. The mechanism underlying the inhibitory effect of HGF was investigated in an in vitro model. We show that HGF markedly antagonizes basal and transforming growth factor (TGF-beta)-... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=1943927 Thu, 06 Nov 2008 05:00:00 +0100 1943927 http://www.medworm.com/index.php?rid=1943926&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%3D18988921%26dopt%3DAbstract In conclusion, intranasal administration of unfractionated bone marrow cells to newborn mice does not achieve epithelial reconstitution but establishes persistent alveolar macrophage chimerism. The predominantly adverse effects of marrow treatment in newborn lungs are likely due to macrophage-associated paracrine effects. While this model and route of cell therapy may not achieve epithelial reconstitution, the role of selected stem cell populations and/or alternate routes of administration for cell-based therapy in injured newborn lungs deserve further investigation. PMID: 18988921 [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=1943926 Thu, 06 Nov 2008 05:00:00 +0100 1943926 http://www.medworm.com/index.php?rid=1943925&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%3D18988922%26dopt%3DAbstract Authors: Cai S, Zemans RL, Young SK, Worthen GS, Jeyaseelan S Bacterial pneumonia remains a serious disease. Pattern recognition receptors play an integral role in neutrophil accumulation during pneumonia. Although MD-2 has been recognized as a key molecule for LPS signaling, the role of MD-2 in neutrophil accumulation in the lung during bacterial infection has not been explored. Here, we investigated the role of MD-2 in E. coli LPS-induced lung inflammation and E. coli-induced pneumonia. LPS-induced CD14-independent neutrophil accumulation was abolished in CD-14/MD-2-/- mice. MD-2-/- mice challenged with LPS displayed attenuated neutrophil influx, NF-kB activation, cytokine/chemokine expression, and lung histolopathology. MD-2-/- mice transplanted with MD-2+/+ bone marrow demonstrate ... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=1943925 Thu, 06 Nov 2008 05:00:00 +0100 1943925 http://www.medworm.com/index.php?rid=1887027&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%3D18927350%26dopt%3DAbstract Authors: Aluwihare P, Munger JS PMID: 18927350 [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=1887027 Sat, 18 Oct 2008 14:21:48 +0100 1887027 http://www.medworm.com/index.php?rid=1887026&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%3D18927351%26dopt%3DAbstract Authors: Abraham E, Adler KB, Shapiro SD, Leff AR PMID: 18927351 [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=1887026 Sat, 18 Oct 2008 14:21:45 +0100 1887026 http://www.medworm.com/index.php?rid=1887025&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%3D18927352%26dopt%3DAbstract Authors: Druilhe A PMID: 18927352 [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=1887025 Sat, 18 Oct 2008 14:21:38 +0100 1887025 http://www.medworm.com/index.php?rid=1887031&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%3D18927346%26dopt%3DAbstract Authors: Matsubara S, Takeda K, Jin N, Okamoto M, Matsuda H, Shiraishi Y, Park JW, McConville G, Joetham A, O'Brien RL, Dakhama A, Born WK, Gelfand EW gammadelta T cells regulate airway reactivity but their role in ozone (O3)-induced airway hyperresponsiveness (AHR) is not known. Different strains of mice including those that were genetically-manipulated or antibody-depleted to render them deficient in total gammadelta T cells or specific subsets of gammadelta T cells were exposed to 2.0 ppm of O3 for 3 hrs. Exposure of C57BL/6 mice to O3 resulted in a transient increase in airway reactivity, neutrophilia, and increased numbers of epithelial cells in the lavage fluid. TCR-delta-/- mice did not develop airway hyperresponsiveness, although they exhibited an increase in neutrophils and ep... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=1887031 Thu, 16 Oct 2008 04:00:00 +0100 1887031 http://www.medworm.com/index.php?rid=1887030&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%3D18927347%26dopt%3DAbstract Authors: Adenuga D, Yao H, March TH, Seagrave J, Rahman I Cigarette smoke (CS)-induced lung inflammation involves the reduction of histone deacetylase (HDAC2) abundance which is associated with steroid resistance in patients with COPD and severe asthmatics who smoke cigarettes. However, the molecular mechanism of cigarette smoke-mediated reduction of HDAC2 is not clearly known. We hypothesized that HDAC2 is phosphorylated and subsequently degraded by the proteasome in vitro in macrophages (MonoMac6), human bronchial and primary small airway epithelial cells, and in vivo in mouse lungs in response to chronic CS exposure. Cigarette smoke extract (CSE) exposure in MonoMac6, bronchial and airway epithelial cells led to phosphorylation of HDAC2 on serine/threonine residues by a protein case... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=1887030 Thu, 16 Oct 2008 04:00:00 +0100 1887030 http://www.medworm.com/index.php?rid=1887029&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%3D18927348%26dopt%3DAbstract Authors: Moghaddam SJ, Li H, Cho SN, Dishop MK, Wistuba II, Ji L, Kurie JM, Dickey BF, Demayo FJ Lung cancer is the leading cause of cancer deaths in the United States. In addition to genetic abnormalities induced by cigarette smoke, several epidemiologic studies have found that smokers with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lungs, have an increased risk of lung cancer (1.3-4.9 fold) compared to smokers without COPD. This suggests a link between chronic airway inflammation and lung carcinogenesis independent of tobacco smoke exposure. We studied this association by assaying the inflammatory impact of products of nontypeable Haemophilus influenzae (NTHi), which colonizes the airways of COPD patients, on lung cancer promotion in mice with an act... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=1887029 Thu, 16 Oct 2008 04:00:00 +0100 1887029 http://www.medworm.com/index.php?rid=1887028&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%3D18927349%26dopt%3DAbstract Authors: Nie HG, Tucker T, Su XF, Na T, Peng JB, Smith PR, Idell S, Ji HL Pleural effusions are commonly clinical disorders, resulting from the imbalance between pleural fluid turnover and re-absorption. The mechanisms underlying pleural fluid clearance across the mesothelium remain to be elucidated. We hypothesized that ENaC is expressed and forms the molecular basis of the amiloride-sensitive resistance in human mesothelial cells. Our RT-PCR results showed that four ENaC subunits, namely, [alpha], [beta], [gamma], and two [delta] ENaC subunits are expressed in human primary pleural mesothelial cells, a human mesothelioma cell line (M9K), and mouse pleural tissue. In addition, Western blotting and immunofluorescence microscopy studies revealed that [alpha], [beta], [gamma], and [delta... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=1887028 Thu, 16 Oct 2008 04:00:00 +0100 1887028 http://www.medworm.com/index.php?rid=1873502&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%3D18849563%26dopt%3DAbstract Authors: Bhattacharya S, Srisuma S, Demeo DL, Shapiro SD, Bueno R, Silverman EK, Reilly JJ, Mariani TJ Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disorder with complex pathological features and largely unknown etiology. The identification of biomarkers for this disease could aid the development of methods to facilitate earlier diagnosis, the classification of disease subtypes and provide a means to define therapeutic response. In order to identify gene expression biomarkers, we completed expression profiling of RNA derived from the lung tissue of 56 subjects with varying degrees of airflow obstruction using the Affymetrix U133 Plus 2.0 array. We applied multiple, independent analytical methods to define biomarkers for either discrete or quantitative disease ph... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=1873502 Fri, 10 Oct 2008 04:00:00 +0100 1873502 http://www.medworm.com/index.php?rid=1856838&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%3D18836136%26dopt%3DAbstract Authors: Alcorn JF, van der Velden J, Brown AL, McElhinney B, Irvin CG, Janssen-Heininger YM Collagen deposition is observed in a diverse set of pulmonary diseases, and the unraveling of the molecular signaling pathways that facilitate collagen deposition represents an ongoing area of investigation. The stress-activated protein kinase, c-Jun N-terminal kinase 1 is activated by a large variety of cellular stresses and environmental insults. Recent work from our laboratory demonstrated the critical role of JNK1 in epithelial to mesenchymal transition. The goal of the present study was to examine the involvement of JNK1 in subepithelial collagen deposition in mice subjected to models of allergic airways disease and interstitial pulmonary fibrosis. Activation of JNK was slightly enhanced i... American Journal of Respiratory Cell and Molecular Biology journals http://www.medworm.com/rss/comments.php?id=1856838 Fri, 03 Oct 2008 04:00:00 +0100 1856838