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Source: European Respiratory Journal
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Total 164 results found since Jan 2013.
Accelerating lung epithelial cell senescence in reduced CARM1 mice enhances elastase-induced emphysema
Emphysema, a key feature of chronic obstructive pulmonary disease is characterized by progressive destruction of pulmonary alveoli. Emphysema development involves alveolar senescence. CARM1, an arginine methyltransferase and transcriptional cofactor, methylating histone and non-histone proteins found crucial for regulating senescence (Wang, BMC Mol Biol 2013). We therefore, hypothesized that loss of CARM1 induces alveolar epithelial cell senescence and thus enhances the susceptibility to elastase-induced emphysema.Porcine pancreatic elastase (PPE) treated C57BL/6 (WT) or CARM1+/- mice were analyzed for lung function, histo...
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Sarker, R. S. J., Bohla, A., Amarie, O. V., Eickelberg, O., Yildirim, A. O. Tags: 3.3 Mechanisms of Lung Injury and Repair Source Type: research
Fibroblast-derived non-canonical WNT ligands contribute to attenuated alveolar epithelial repair in COPD
Conclusion: In COPD, attenuated canonical WNT signaling and disturbed alveolar epithelial cell repair may be a consequence of a shift in conditions that triggers WNT-5A secretion by fibroblasts.
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Baarsma, H. A., Boczkowski, J., Yildirim, A. O., Konigshoff, M. Tags: 3.3 Mechanisms of Lung Injury and Repair Source Type: research
Reduction of high mobility group nucleosome binding domain-5 protein promotes the development of emphysema
Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation which is associated with an enhanced chronic inflammation and development of emphysema. However, the mechanism by which genetic alteration contributes to empyhsema development is still barely understood. In a previous study we have detected spontaneous emphysema development in HMGN5 knockout mice (Kluger E.J., et. al., JBC 2013). The HMGN5 gene encodes a nucleosomal binding protein that competes with H1 on the nucleosome and loosens the structure of chromatin. It plays an important role in transcription, replication and the repair mechanism...
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Merthan, L., Bustin, M., Eickelberg, O., Yildirim, A. O. Tags: 3.3 Mechanisms of Lung Injury and Repair Source Type: research
Protein tyrosine phosphatase PTPRR regulates PP2A in mononuclear cells
Conclusion: We have demonstrated that reduction of PTPRR down-regulates PP2AC via enhancement of PP2AC-Tyr307 phosphorylation that may lead to corticosteroid insensitivity. This novel mechanism may be a new therapeutic target for restoration of corticosteroid sensitivity in patients with severe asthma.
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Kobayashi, Y., Miller-Larsson, A., Ito, K., Kanda, A., Tomoda, K., Barnes, P. J., Mercado, N. Tags: 3.2 Airway Cell Biology and Immunopathology Source Type: research
LSC 2014 abstract - ROR{gamma} t-specific RNAi decreases allergic airway inflammation and airway hyperresponsiveness in a mouse model of neutrophilic asthma
Conclusion: Our data show that knockdown of ROR t by gene silencing improved airway inflammation in a mouse model of experimental asthma and may have therapeutic potential for the treatment of neutrophilic asthma.
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Webering, S., Lunding, L., Fehrenbach, H., Wegmann, M. Tags: 5.3 Allergy and Immunology Source Type: research
Late-breaking abstract: The effects and mechanism of adiponectin on inhibiting pulmonary fibrosis
Conclusions Overall, these studies indicated some protective effects of APN on PQ induced pulmonary fibrosis in a dose-dependent manner. There are APN and functional AdipoR1 expressed by human WI-38 lung fibroblasts, suggesting a potential application prospect of APN for lung fibrosis.
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Yao, R., Cao, Y., He, Y.-r., Zeng, Z., Liang, Z.-a. Tags: 1.5 Diffuse Parenchymal Lung Disease Source Type: research
Late-breaking abstract: Inhibition of RC kinase is a novel therapeutic approach for the treatment of COPD and IPF
RC kinase is a novel serine/threonine kinase, expressed predominantly by pulmonary macrophage and type II bronchial epithelial cells. Examination of BAL macrophage mRNA isolated from COPD and IPF patients showed increased expression of RC kinase compared to normal smokers and non-smoking patients. In vitro studies showed an upregulation of RC kinase upon cell stress, including oxidative stress. This correlated with an increase of NF-kb activity and IL-8 production that could be inhibited by RC kinase siRNA or small molecule antagonists. Biochemical analysis revealed that RC kinase is predominantly a nuclear protein and int...
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Boehme, S., Coelho, A., Hogaboam, C., Ly, T. W., Bacon, K., Athanacio, J. Tags: 5.1 Airway Pharmacology and Treatment Source Type: research
LSC 2014 abstract - Influenza infection of human lung macrophages increases PDL1 expression via autologous IFN{beta}
Lung macrophages are an important defence against influenza infection, but macrophage function can be dysregulated by infection. Recent work has shown that acute immune responses to influenza in the murine lung are regulated by PDL1 expression leading to rapid modulation of CD8+ T cell responses via the PD1 receptor1. This PD1/PDL1 pathway may modulate acute inflammatory responses to prevent tissue damage. The aim of the present study was to investigate how human macrophages regulate their PDL1 expression in response to influenza infection. Human lung and monocyte-derived macrophages (MDMs) were exposed to H3N2 X31 influen...
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Staples, K., Spalluto, C. M., McKendry, R. T., Wilkinson, T. M. A. Tags: 10.1 Respiratory Infections Source Type: research
Loss of PTEN induced lung fibroblasts exhibiting similar pathogenic features to cancer cells in idiopathic pulmonary fibrosis
Conclusion: These findings indicate that lung fibroblasts have decreased PTEN expression in IPF. Inhibition of PTEN induced fibroblast activation and exhibiting similar pathogenic features to cancer cells.
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Geng, J., Huang, X., Dai, H. Tags: 1.5 Diffuse Parenchymal Lung Disease Source Type: research
Activation of PI3K-d signaling pathway contributes to the generation of mitochondrial ROS and NLRP3 inflammasome in HDM-inhaled mice
In this study, we have investigated the effects of IC87114, a representative inhibitor of PI3K- isoform, on the HDM-induced airway inflammation and hyperresponsiveness. In addition, we tried to define the role of PI3K- in the HDM-induced NLRP3 inflammasome activation in airways using primary cultured tracheal epithelial cells.HDM-sensitized and -challenged mice showed the typical allergic airway inflammation and hyperresponsivenss, and the increased levels of Th2 cytokines, IL-17, IL-1β, and TNF-α in lungs. Moreover, we found the increases of mitochondrial ROS and the NLRP3 inflammasome activation in HDM-exposed...
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Kim, S. R., Lee, Y. C., Lee, K. B., Kim, D. I. Tags: 5.3 Allergy and Immunology Source Type: research
Phosphoinositide 3-kinase {delta} signaling modulates endoplasmic reticulum stress in aspergillus fumigatus-induced allergic lung inflammation
In this study, we aimed to elucidate an association of ER stress with PI3K- signaling in fungus-induced allergic lung inflammation.Using Aspergillus fumigatus-exposed in vivo and in vitro experimental systems, we have investigated the role of PI3K- in the regulation of ER stress in the pathogenesis of allergic lung inflammation.The Aspergillus fumigatus-sensitized and -challenged mice showed that the expression of ER stress markers and the protein levels of unfolded protein response (UPR)-related markers in lung tissues were significantly increased after Aspergillus fumigatus challenge. Protein expression of ER stress mark...
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Lee, Y. C., Kim, S. R., Lee, K. S., Ko, Y. H., Jeong, J. S. Tags: 5.3 Allergy and Immunology Source Type: research
Smad1 deficiency and female gender contribute to the development of pulmonary hypertension
Conclusions. These findings suggest that the presence of female hormones, coupled with Smad1 deficiency plays a role in the female susceptibility to develop PH.
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Mair, K., Yang, X., Long, L., White, K., Nilsen, M., Morrell, N., MacLean, M. R. Tags: 4.3 Pulmonary Circulation and Pulmonary Vascular Disease Source Type: research
Late-breaking abstract: The bromodomain-containing protein 4: The epigenetic origin of the oncogenic signature in pulmonary hypertension
Conclusion: Our study suggests an important role for BRD4 in pulmonary hypertension and opens the door to new avenues of investigation and proposes BRD4 as putative treatment for PAH.
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Vaillancourt, M., Meloche, J., Ferraro, P., Provencher, S., Bonnet, S. Tags: 4.3 Pulmonary Circulation and Pulmonary Vascular Disease Source Type: research
Role of hypoxia in epithelial-to-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC)
Conclusion : Hypoxia seems to induce a partial EMT phenotype in NSCLC cell lines harboring EGFR mutation, in part related to HIF-1α expression.
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Renaud, S., Guenot, D., Falcoz, P.-E., Massard, G., Beau-Faller, M. Tags: 3.1 Molecular Pathology and Functional Genomics Source Type: research
Proteasome function in pulmonary fibrosis
Pathological remodeling processes in IPF critically depend on a proper function of protein homeostasis in lung cells. The proteasome, a multicatalytic protease, is crucial for maintainance of protein homeostasis. It consists of a catalytic core (20S) and a regulator (19S), together forming highly active 26S proteasomes.Here, we examined the role of the proteasome in myofibroblast differentiation and its dysregulation in the pathogenesis of lung fibrosis.CCL206 lung fibroblasts were treated with TGF-β1 to induce myofibroblast differentiation and proteasome activity was assayed by specific luminescent substrates and nat...
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Semren, N., Korfei, M., Fernandez, I., Gunther, A., Eickelberg, O., Meiners, S. Tags: 3.3 Mechanisms of Lung Injury and Repair Source Type: research
