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Source: AJP: Lung Cellular and Molecular Physiology

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Total 59 results found since Jan 2013.

Fibroblasts that resist cigarette smoke-induced senescence acquire profibrotic phenotypes
This study assessed the effect of extended exposure to cigarette smoke extract (CSE) on tissue repair functions in lung fibroblasts. Human fetal (HFL-1) and adult lung fibroblasts were exposed to CSE for 14 days. Senescence-associated β-galactosidase (SA β-gal) expression, cell proliferation, and tissue repair functions including chemotaxis and gel contraction were assessed. HFL-1 proliferation was inhibited by CSE and nearly half of the CSE-exposed cells were SA β-gal positive after 14 days exposure, whereas 33% of adult lung fibroblasts were SA β-gal positive in response to 10% CSE exposure. The SA &b...
Source: AJP: Lung Cellular and Molecular Physiology - September 1, 2014 Category: Respiratory Medicine Authors: Kanaji, N., Basma, H., Nelson, A., Farid, M., Sato, T., Nakanishi, M., Wang, X., Michalski, J., Li, Y., Gunji, Y., Feghali-Bostwick, C., Liu, X., Rennard, S. I. Tags: ARTICLES Source Type: research

Silencing Bruton's tyrosine kinase in alveolar neutrophils protects mice from LPS/immune complex-induced acute lung injury
In conclusion, we put forward a hypothesis that Btk-targeted neutrophil specific therapy is a valid goal of research geared toward restoring homeostasis in lungs of patients with ALI/ARDS.
Source: AJP: Lung Cellular and Molecular Physiology - September 15, 2014 Category: Respiratory Medicine Authors: Krupa, A., Fol, M., Rahman, M., Stokes, K. Y., Florence, J. M., Leskov, I. L., Khoretonenko, M. V., Matthay, M. A., Liu, K. D., Calfee, C. S., Tvinnereim, A., Rosenfield, G. R., Kurdowska, A. K. Tags: CALL FOR PAPERS Source Type: research

Promotion of lung tumor growth by interleukin-17
Recent findings demonstrate that inhaled cigarette smoke, the predominant lung carcinogen, elicits a T helper 17 (Th17) inflammatory phenotype. Interleukin-17A (IL-17), the hallmark cytokine of Th17 inflammation, displays pro- and antitumorigenic properties in a manner that varies according to tumor type and assay system. To investigate the role of IL-17 in lung tumor growth, we used an autochthonous tumor model (K-RasLA1 mice) with lung delivery of a recombinant adenovirus that expresses IL-17A. Virus-mediated expression of IL-17A in K-RasLA1 mice at 8–10 wk of age doubled lung tumor growth in 3 wk relative to litte...
Source: AJP: Lung Cellular and Molecular Physiology - September 15, 2014 Category: Respiratory Medicine Authors: Xu, B., Guenther, J. F., Pociask, D. A., Wang, Y., Kolls, J. K., You, Z., Chandrasekar, B., Shan, B., Sullivan, D. E., Morris, G. F. Tags: ARTICLES Source Type: research

GSK3{beta}-dependent inhibition of AMPK potentiates activation of neutrophils and macrophages and enhances severity of acute lung injury
Although AMP-activated protein kinase (AMPK) is involved in regulating carbohydrate and lipid metabolism, activated AMPK also plays an anti-inflammatory role in many cell populations. However, despite the ability of AMPK activation to diminish the severity of inflammatory responses, previous studies have found that AMPK activity is diminished in LPS-treated neutrophils and also in lungs of mice with LPS-induced acute lung injury (ALI). Since GSK3β participates in regulating AMPK activity, we examined potential roles for GSK3β in modulating LPS-induced activation of neutrophils and macrophages and in influencing s...
Source: AJP: Lung Cellular and Molecular Physiology - November 15, 2014 Category: Respiratory Medicine Authors: Park, D. W., Jiang, S., Liu, Y., Siegal, G. P., Inoki, K., Abraham, E., Zmijewski, J. W. Tags: CALL FOR PAPERS Source Type: research

Impaired TLR4 and HIF expression in cystic fibrosis bronchial epithelial cells downregulates hemeoxygenase-1 and alters iron homeostasis in vitro
In this study, we investigated in vitro the role of Toll-like receptor 4 (TLR4), hypoxia-inducible factor 1α (HIF-1α), and iron on HO-1 expression in cystic fibrosis (CF). Immunohistochemical analysis of TLR4, HO-1, ferritin, and HIF-1α were performed on lung sections of CFTR–/– and wild-type mice. CFBE41o- and 16HBE14o- cell lines were employed for in vitro analysis via immunoblotting, immunofluorescence, real-time PCR, luciferase reporter gene analysis, and iron quantification. We observed a reduced TLR4, HIF-1α, HO-1, and ferritin in CFBE41o- cell line and CF mice. Knockdown studies u...
Source: AJP: Lung Cellular and Molecular Physiology - November 15, 2014 Category: Respiratory Medicine Authors: Chillappagari, S., Venkatesan, S., Garapati, V., Mahavadi, P., Munder, A., Seubert, A., Sarode, G., Guenther, A., Schmeck, B. T., Tummler, B., Henke, M. O. Tags: ARTICLES Source Type: research

Nox2-dependent glutathionylation of endothelial NOS leads to uncoupled superoxide production and endothelial barrier dysfunction in acute lung injury
This study was designed to investigate how eNOS-dependent superoxide production contributes to endothelial barrier dysfunction in inflammatory lung injury and its regulation. C57BL/6J mice were challenged with intratracheal LPS. Bronchoalveolar lavage fluid was analyzed for protein accumulation, and lung tissue homogenate was assayed for endothelial NOS content and function. Human lung microvascular endothelial cell (HLMVEC) monolayers were exposed to LPS in vitro, and barrier integrity and superoxide production were measured. Biopterin species were quantified, and coimmunoprecipitation (Co-IP) assays were performed to ide...
Source: AJP: Lung Cellular and Molecular Physiology - December 15, 2014 Category: Respiratory Medicine Authors: Wu, F., Szczepaniak, W. S., Shiva, S., Liu, H., Wang, Y., Wang, L., Wang, Y., Kelley, E. E., Chen, A. F., Gladwin, M. T., McVerry, B. J. Tags: ARTICLES Source Type: research

Differential and opposing effects of imatinib on LPS- and ventilator-induced lung injury
Endothelial dysfunction underlies the pathophysiology of vascular disorders such as acute lung injury (ALI) syndromes. Recent work has identified the Abl family kinases (c-Abl and Arg) as important regulators of endothelial cell (EC) barrier function and suggests that their inhibition by currently available pharmaceutical agents such as imatinib may be EC protective. Here we describe novel and differential effects of imatinib in regulating lung pathophysiology in two clinically relevant experimental models of ALI. Imatinib attenuates endotoxin (LPS)-induced vascular leak and lung inflammation in mice but exacerbates these ...
Source: AJP: Lung Cellular and Molecular Physiology - February 1, 2015 Category: Respiratory Medicine Authors: Letsiou, E., Rizzo, A. N., Sammani, S., Naureckas, P., Jacobson, J. R., Garcia, J. G. N., Dudek, S. M. Tags: CALL FOR PAPERS Source Type: research

Pulmonary artery smooth muscle cell endothelin-1 expression modulates the pulmonary vascular response to chronic hypoxia
Endothelin-1 (ET-1) increases pulmonary vascular tone through direct effects on pulmonary artery smooth muscle cells (PASMC) via membrane-bound ET-1 receptors. Circulating ET-1 contributes to vascular remodeling by promoting SMC proliferation and migration and inhibiting SMC apoptosis. Although endothelial cells (EC) are the primary source of ET-1, whether ET-1 produced by SMC modulates pulmonary vascular tone is unknown. Using transgenic mice created by crossbreeding SM22α-Cre mice with ET-1 flox/flox mice to selectively delete ET-1 in SMC, we tested the hypothesis that PASMC ET-1 gene expression modulates the pulmo...
Source: AJP: Lung Cellular and Molecular Physiology - February 15, 2015 Category: Respiratory Medicine Authors: Kim, F. Y., Barnes, E. A., Ying, L., Chen, C., Lee, L., Alvira, C. M., Cornfield, D. N. Tags: CALL FOR PAPERS Source Type: research

p53 protects against LPS-induced lung endothelial barrier dysfunction
New therapies toward heart and blood vessel disorders may emerge from the development of Hsp90 inhibitors. Several independent studies suggest potent anti-inflammatory activities of those agents in human tissues. The molecular mechanisms responsible for their protective effects in the vasculature remain unclear. The present study demonstrates that the transcription factor p53, an Hsp90 client protein, is crucial for the maintenance of vascular integrity, protects again LPS-induced endothelial barrier dysfunction, and is involved in the mediation of the anti-inflammatory activity of Hsp90 inhibitors in lung tissues. p53 sil...
Source: AJP: Lung Cellular and Molecular Physiology - April 15, 2015 Category: Respiratory Medicine Authors: Barabutis, N., Dimitropoulou, C., Birmpas, C., Joshi, A., Thangjam, G., Catravas, J. D. Tags: CALL FOR PAPERS Source Type: research

Influence of glutathione-S-transferase (GST) inhibition on lung epithelial cell injury: role of oxidative stress and metabolism
Oxidant-mediated tissue injury is key to the pathogenesis of acute lung injury. Glutathione-S-transferases (GSTs) are important detoxifying enzymes that catalyze the conjugation of glutathione with toxic oxidant compounds and are associated with acute and chronic inflammatory lung diseases. We hypothesized that attenuation of cellular GST enzymes would augment intracellular oxidative and metabolic stress and induce lung cell injury. Treatment of murine lung epithelial cells with GST inhibitors, ethacrynic acid (EA), and caffeic acid compromised lung epithelial cell viability in a concentration-dependent manner. These inhib...
Source: AJP: Lung Cellular and Molecular Physiology - June 15, 2015 Category: Respiratory Medicine Authors: Fletcher, M. E., Boshier, P. R., Wakabayashi, K., Keun, H. C., Smolenski, R. T., Kirkham, P. A., Adcock, I. M., Barton, P. J., Takata, M., Marczin, N. Tags: ARTICLES Source Type: research

Endothelin-1 induces VCAM-1 expression-mediated inflammation via receptor tyrosine kinases and Elk/p300 in human tracheal smooth muscle cells
The elevated level of endothelin-1 (ET-1) has been detected in the bronchoalveolar lavage of patients with severe asthma, acute lung injury, acute respiratory distress syndrome, and sepsis. ET-1 may affect vessel tone together with lung physiology and pathology. Vascular cell adhesion molecule-1 (VCAM-1) is one kind of adhesion molecules participating in the process of polymorphonuclear leukocyte transmigration and regulating the occurrence and amplification of tissue inflammation. However, the molecular mechanisms underlying ET-1-mediated expression of VCAM-1 on human tracheal smooth muscle cells (HTSMCs) were largely unk...
Source: AJP: Lung Cellular and Molecular Physiology - August 1, 2015 Category: Respiratory Medicine Authors: Lin, C.-C., Lin, W.-N., Hou, W.-C., Hsiao, L.-D., Yang, C.-M. Tags: CALL FOR PAPERS Source Type: research

Human airway smooth muscle cells secrete amphiregulin via bradykinin/COX-2/PGE2, inducing COX-2, CXCL8, and VEGF expression in airway epithelial cells
Human airway smooth muscle cells (HASMC) contribute to asthma pathophysiology through an increased smooth muscle mass and elevated cytokine/chemokine output. Little is known about how HASMC and the airway epithelium interact to regulate chronic airway inflammation and remodeling. Amphiregulin is a member of the family of epidermal growth factor receptor (EGFR) agonists with cell growth and proinflammatory roles and increased expression in the lungs of asthma patients. Here we show that bradykinin (BK) stimulation of HASMC increases amphiregulin secretion in a mechanism dependent on BK-induced COX-2 expression, increased PG...
Source: AJP: Lung Cellular and Molecular Physiology - August 1, 2015 Category: Respiratory Medicine Authors: Deacon, K., Knox, A. J. Tags: CALL FOR PAPERS Source Type: research

IFN-{gamma}-induced JAK/STAT, but not NF-{kappa}B, signaling pathway is insensitive to glucocorticoid in airway epithelial cells
Although the majority of patients with asthma are well controlled by inhaled glucocorticoids (GCs), patients with severe asthma are poorly responsive to GCs. This latter group is responsible for a disproportionate share of health care costs associated with asthma. Recent studies in immune cells have incriminated interferon- (IFN-) as a possible trigger of GC insensitivity in severe asthma; however, little is known about the role of IFN- in modulating GC effects in other clinically relevant nonimmune cells, such as airway epithelial cells. We hypothesized that IFN--induced JAK/STAT-associated signaling pathways in airway ep...
Source: AJP: Lung Cellular and Molecular Physiology - August 15, 2015 Category: Respiratory Medicine Authors: O'Connell, D., Bouazza, B., Kokalari, B., Amrani, Y., Khatib, A., Ganther, J. D., Tliba, O. Tags: CALL FOR PAPERS Source Type: research

Pharmacologic inhibition of lactate production prevents myofibroblast differentiation
Myofibroblasts are one of the primary cell types responsible for the accumulation of extracellular matrix in fibrosing diseases, and targeting myofibroblast differentiation is an important therapeutic strategy for the treatment of pulmonary fibrosis. Transforming growth factor-β (TGF-β) has been shown to be an important inducer of myofibroblast differentiation. We previously demonstrated that lactate dehydrogenase and its metabolic product lactic acid are important mediators of myofibroblast differentiation, via acid-induced activation of latent TGF-β. Here we explore whether pharmacologic inhibition of LDH ...
Source: AJP: Lung Cellular and Molecular Physiology - December 1, 2015 Category: Respiratory Medicine Authors: Kottmann, R. M., Trawick, E., Judge, J. L., Wahl, L. A., Epa, A. P., Owens, K. M., Thatcher, T. H., Phipps, R. P., Sime, P. J. Tags: CALL FOR PAPERS Source Type: research

Hydrogen peroxide-induced calcium influx in lung microvascular endothelial cells involves TRPV4
In conclusion, our data suggest that application of exogenous H2O2 increases [Ca2+]i and decreases TER in microvascular endothelial cells via activation of TRPV4 through a mechanism that requires the Src kinase Fyn.
Source: AJP: Lung Cellular and Molecular Physiology - December 15, 2015 Category: Respiratory Medicine Authors: Suresh, K., Servinsky, L., Reyes, J., Baksh, S., Undem, C., Caterina, M., Pearse, D. B., Shimoda, L. A. Tags: CALL FOR PAPERS Source Type: research