Document Detail


Role of IL-18 in second-hand smoke-induced emphysema.
MedLine Citation:
PMID:  23392573     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic second-hand smoke (SHS) exposure comprises the main risk factor for nonsmokers to develop chronic obstructive pulmonary disease (COPD). However, the mechanisms behind the chronic inflammation and lung destruction remain incompletely understood. In this study, we show that chronic exposure of Sprague-Dawley rats to SHS results in a significant increase of proinflammatory cytokine IL-18 and chemokine (C-C motif) ligand 5 in the bronchoalveolar lavage fluid (BALF) and a significant decrease of vascular endothelial growth factor (VEGF) in the lung tissue. SHS exposure resulted in progressive alveolar airspace enlargement, cell death, pulmonary vessel loss, vessel muscularization, collagen deposition, and right ventricular hypertrophy. Alveolar macrophages displayed a foamy phenotype and a decreased expression of the natural inhibitor of IL-18, namely, IL-18 binding protein (IL-18BP). Moreover, IL-18 down-regulated the expression of VEGF receptor-1 and VEGFR receptor-2, and induced apoptosis in pulmonary microvascular endothelial cells in vitro. We also observed a trend toward increased concentrations of IL-18 in the BALF of patients with COPD. Our findings suggest that IL-18-mediated endothelial cell death may contribute to vascular destruction and disappearance in SHS-induced COPD. Moreover, IL-18 and IL-18BP are potential new targets for therapeutics.
Authors:
Adelheid Kratzer; Jonas Salys; Claudia Nold-Petry; Carlyne Cool; Martin Zamora; Russ Bowler; Andreas Rembert Koczulla; Sabina Janciauskiene; Michael G Edwards; Charles A Dinarello; Laimute Taraseviciene-Stewart
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  48     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-06-04     Completed Date:  2013-08-05     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  725-32     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Bronchoalveolar Lavage Fluid / immunology
Capillary Permeability
Cardiomegaly / chemically induced,  pathology
Cell Death
Cell Line
Chemokine CCL5 / immunology
Endothelial Cells / immunology,  metabolism,  pathology*
Humans
Immunohistochemistry
Inhalation Exposure / adverse effects
Intercellular Signaling Peptides and Proteins / genetics,  immunology,  metabolism
Interleukin-18 / genetics,  immunology*,  metabolism
Macrophages, Alveolar / immunology,  pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Pulmonary Disease, Chronic Obstructive / immunology,  pathology
Pulmonary Emphysema / immunology,  pathology*
Pulmonary Fibrosis / chemically induced,  pathology
Rats
Rats, Sprague-Dawley
Tobacco Products / adverse effects
Tobacco Smoke Pollution / adverse effects*
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-1 / genetics,  metabolism
Vascular Endothelial Growth Factor Receptor-2 / genetics,  metabolism
Weight Loss
Grant Support
ID/Acronym/Agency:
AI 15614/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Chemokine CCL5; 0/Intercellular Signaling Peptides and Proteins; 0/Interleukin-18; 0/Tobacco Smoke Pollution; 0/Vascular Endothelial Growth Factor A; 0/interleukin-18 binding protein; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-1; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2
Comments/Corrections
Erratum In:
Am J Respir Cell Mol Biol. 2014 Feb;50(2):470

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