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Source: American Journal of Physiology. Lung Cellular and Molecular Physiology

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Total 135 results found since Jan 2013.

IFNγ-induced JAK/STAT-, but not NF-κB-, signaling pathway is insensitive to glucocorticoid in airway epithelial cells.
Abstract Although the majority of asthmatics are well controlled by inhaled glucocorticoids (GCs), severe asthmatics are poorly responsive to GCs. This latter group is responsible for a disproportionate share of healthcare costs associated with asthma. Recent studies in immune cells have incriminated interferon gamma (IFNγ) as a possible trigger of GC insensitivity in severe asthma; however, little is known about the role of IFNγ in modulating GC effects in other clinically relevant non-immune cells, such as airway epithelial cells. We hypothesized that IFNγ-induced JAK/STAT-associated signaling pathways in air...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - June 19, 2015 Category: Cytology Authors: O'Connell D, Bouazza B, Kokalari B, Amrani Y, Khatib A, Ganther JD, Tliba O Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Endothelin-1 Induces VCAM-1 Expression-Mediated Inflammation via Receptor Tyrosine Kinases and Elk/p300 in Human Tracheal Smooth Muscle Cells.
Abstract 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 leukocytes 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 (HTSMC...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - June 12, 2015 Category: Cytology Authors: Lin CC, Lin WN, Hou WC, Hsiao L, Yang CM Tags: Am J Physiol Lung Cell Mol Physiol 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.
Abstract 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 remodelling. Amphiregulin is a member of the family of epidermal growth factor receptor (EGFR) agonists with cell growth and pro-inflammatory 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 upon BK induced COX-2 ex...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - June 5, 2015 Category: Cytology Authors: Deacon K, Knox AJ Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

C-Abl mediated tyrosine phosphorylation of paxillin regulates LPS-induced endothelial dysfunction and lung injury.
Abstract Paxillin is phosphorylated at multiple residues; however, the role of tyrosine phosphorylation of paxillin in endothelial barrier dysfunction and acute lung injury (ALI) remains unclear. We used siRNA and site specific non-phosphorylable mutants of paxillin to abrogate the function of paxillin to determine its role in lung endothelial permeability and ALI. In vitro, lipopolysaccharide (LPS) challenge of human lung microvascular endothelial cells (HLMVECs) resulted in enhanced tyrosine phosphorylation of paxillin at Y31 and Y118 with no significant change in Y181 and significant barrier dysfunction. Knockd...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 20, 2015 Category: Cytology Authors: Fu P, Usatyuk PV, Lele A, Harijith A, Gregorio CC, Garcia JG, Salgia R, Natarajan V Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Silencing of MUC8 by siRNA increases P2Y2-induced airway inflammation.
Abstract Mucin hypersecretion and overproduction are frequent manifestations of respiratory disease. Determining the physiological function of airway mucin is presently considered more important than identifying the relevant signaling pathways. The lack of a full-length human MUC8 cDNA sequence has hindered the generation of a Muc8 knockout mouse line. Thus, the precise physiological functions of MUC8 are unclear. Herein, we investigated the function of MUC8 using a siRNA-mediated genetic silencing approach in human airway epithelial cells. Herein, intracellular IL-1α production was stimulated by an ATP/P2Y2 comp...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - January 9, 2015 Category: Cytology Authors: Cha HJ, Jung MS, Ahn DW, Choi JK, Ock MS, Kim KS, Yoon JH, Song EJ, Song KS Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Pulmonary artery smooth muscle cell endothelin-1 expression modulates the pulmonary vascular response to chronic hypoxia.
Abstract Endothelin-1 (ET-1) increases pulmonary vascular tone through effects on pulmonary artery smooth muscle cells (PASMC) via membrane bound ET-1 receptors. Circulating ET-1 causes vascular remodeling by promoting SMC proliferation, migration, and inhibiting SMC apoptosis. While 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 SMC ET-1 , we tested the hypothesis that PASMC ET-1 gene expression modulates the pulmonary va...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - November 14, 2014 Category: Cytology Authors: Kim FY, Barnes EA, Ying L, Chen C, Lee L, Alvira CM, Cornfield DN Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Nox2-dependent glutathionylation of endothelial NOS leads to uncoupled su-peroxide 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 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 co-immunoprecipitation (Co-IP) assays were performed to identify...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - October 17, 2014 Category: Cytology Authors: Wu F, Szczepaniak WS, Shiva S, Liu H, Wang Y, Wang L, Wang Y, Kelley EE, Chen AF, Gladwin MT, McVerry BJ Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

GSK3β-dependent inhibition of AMPK potentiates activation of neutrophils and macrophages, and enhances severity of acute lung injury.
Abstract 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, in spite of 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. As GSK3β participates in regulating AMPK activity, we examined potential roles for GSK3β in modulating LPS-induced activation of neutrophils and macrophages, and in influen...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - September 19, 2014 Category: Cytology Authors: Park DW, Jiang S, Liu Y, Siegal GP, Inoki K, Abraham E, Zmijewski JW Tags: Am J Physiol Lung Cell Mol Physiol 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 wildtype 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 using TLR4-siRNA in 16HBE14o- reveale...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - September 19, 2014 Category: Cytology Authors: Chillappagari S, Venkatesan S, Garapati V, Mahavadi P, Munder A, Seubert A, Sarode G, Guenther A, Schmeck BT, Tümmler B, Henke MO Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Dicer mediating the expression of miR-143 and miR-155 regulates hexokinase II associated cellular response to hypoxia.
Abstract Lung alveolar epithelial cells are exposed to hypoxia under a variety of physiological and pathological conditions. It has been shown recently that miR-143, which can directly target the key glycolytic enzyme hexokinase II (HK2), may be regulated by miR-155. We investigated whether microRNAs contribute to the cellular glycolysis in response to hypoxia. Using the A549 cells, we found that the expression of Dicer is decreased under hypoxia. When Dicer was knocked down with siRNA, pre-miR143 was increased and mature miR-143 was decreased as that in hypoxia, indicating that reduction of Dicer is responsible f...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - August 29, 2014 Category: Cytology Authors: Yao M, Wang X, Tang Y, Zhang W, Cui B, Liu Q, Xing L Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Promotion of Lung Tumor Growth by Interleukin-17.
Abstract 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 anti-tumorigenic 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-ras(LA1) mice) with lung delivery of a recombinant adenovirus that expresses IL-17A. Virus-mediated expression of IL-17A in K-Ras(LA1) mice at 8-10 weeks of age doubled lung tumor growth in th...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - July 18, 2014 Category: Cytology Authors: Xu B, Guenther JF, Pociask DA, Wang Y, Kolls JK, You Z, Chandrasekar B, Shan B, Sullivan DE, Morris GF Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Atg7 deficiency impaires host defense against Klebsiella pneumoniae by impacting bacterial clearance, survival and inflammatory responses in mice.
Abstract Klebsiella pneumoniae (Kp) is a Gram-negative bacterium that can cause serious infections in humans. Autophagy-related gene 7 (Atg7) has been implicated in certain bacterial infections; however, the role of Atg7 in macrophage-mediated immunity against Kp infection has not been elucidated. Here we showed that Atg7 expression was significantly increased in murine alveolar macrophages (MH-S) upon Kp infection, indicating that Atg7 participated in host defense. Knocking down Atg7 with siRNA increased bacterial burdens in MH-S cells. Using cell biology assays and whole animal imaging analysis, we found that co...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - July 3, 2014 Category: Cytology Authors: Ye Y, Li X, Wang W, Ouedraogo KC, Li Y, Gan C, Tan S, Zhou X, Wu M Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Matrix metalloproteinase-9 activates TGF-ss and stimulates fibroblast contraction of collagen gels.
This study provides direct evidence that endogenously produced MMP-9 has a role in regulation of tissue contraction of 3-dimensional collagen gels mediated by fibroblasts. PMID: 24705725 [PubMed - as supplied by publisher]
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - April 4, 2014 Category: Cytology Authors: Kobayashi T, Kim H, Liu X, Sugiura H, Kohyama T, Fang Q, Wen FQ, Abe S, Wang X, Atkinson JJ, Shipley JM, Senior RM, Rennard SI Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Transgelin as a Therapeutic Target to Prevent Hypoxic Pulmonary Hypertension.
Abstract We previously observed that transgelin was preferentially expressed in human pulmonary arterial smooth muscle cells (PAMSCs) under hypoxia and that the upregulation of transgelin was independent of hypoxia inducible factor 1α (HIF-1α). Reduced transgelin expression was accompanied by significantly impaired migration ability in vitro. However, the regulation mechanism of transgelin and its function in preventing hypoxic pulmonary hypertension (HPH) was unclear. In the present study, RNA interference with hypoxia inducible factor 2α (HIF-2α) was employed in human PASMCs. Transgelin expression was dimini...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - January 24, 2014 Category: Cytology Authors: Zhang R, Shi L, Zhou L, Zhang G, Wu X, Shao F, Ma G, Ying K Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Endothelin-1 decreases Endothelial PPAR gamma Signaling and Impairs Angiogenesis After Chronic Intrauterine Pulmonary Hypertension.
Abstract Increased endothelin-1 (ET-1) disrupts angiogenesis in persistent pulmonary hypertension of the newborn (PPHN), but pathogenic mechanisms are unclear. PPAR gamma (PPARγ) is decreased in adult pulmonary hypertension, but whether ET-1-PPARγ interactions impair endothelial cell (EC) function and angiogenesis in PPHN remains unknown. We hypothesized that increased PPHN PAEC ET-1 production decreases PPARγ signaling and impairs tube formation in vitro. Proximal PAECs were harvested from fetal sheep after partial ligation of the ductus arteriosus in utero (PPHN) and controls. PPARγ and phospho-PPARγ protei...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - December 13, 2013 Category: Cytology Authors: Wolf D, Tseng N, Seedorf GJ, Roe GB, Abman SH, Gien J Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research