Source:http://linkedlifedata.com/resource/pubmed/id/17237446
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2007-1-22
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pubmed:abstractText |
Th1 inflammation and remodeling characterized by local tissue destruction coexist in pulmonary emphysema and other diseases. To test the hypothesis that IL-18 plays an important role in these responses, we characterized the regulation of IL-18 in lungs from cigarette smoke (CS) and room air-exposed mice and characterized the effects of CS in wild-type mice and mice with null mutations of IL-18Ralpha (IL-18Ralpha(-/-)). CS was a potent stimulator and activator of IL-18 and caspases 1 and 11. In addition, although CS caused inflammation and emphysema in wild-type mice, both of these responses were significantly decreased in IL-18Ralpha(-/-) animals. CS also induced epithelial apoptosis, activated effector caspases and stimulated proteases and chemokines via IL-18Ralpha-dependent pathways. Importantly, the levels of IL-18 and its targets, cathepsins S and B, were increased in pulmonary macrophages from smokers and patients with chronic obstructive lung disease. Elevated levels of circulating IL-18 were also seen in patients with chronic obstructive lung disease. These studies demonstrate that IL-18 and the IL-18 pathway are activated in CS-exposed mice and man. They also demonstrate, in a murine modeling system, that IL-18R signaling plays a critical role in the pathogenesis of CS-induced inflammation and emphysema.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/Smoke
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-1767
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pubmed:author |
pubmed-author:CainHilaryH,
pubmed-author:ChoSoo JungSJ,
pubmed-author:ChuppGeoffreyG,
pubmed-author:CrothersKristina AKA,
pubmed-author:EliasJack AJA,
pubmed-author:GalloAmyA,
pubmed-author:HomerRobert JRJ,
pubmed-author:KangMin-JongMJ,
pubmed-author:LeeChun GeunCG,
pubmed-author:RochesterCarolynC,
pubmed-author:YoonHo JooHJ
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
178
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1948-59
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pubmed:dateRevised |
2007-12-3
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pubmed:meshHeading |
pubmed-meshheading:17237446-Animals,
pubmed-meshheading:17237446-Apoptosis,
pubmed-meshheading:17237446-Caspases,
pubmed-meshheading:17237446-Chemokines,
pubmed-meshheading:17237446-Epithelial Cells,
pubmed-meshheading:17237446-Humans,
pubmed-meshheading:17237446-Inflammation,
pubmed-meshheading:17237446-Interleukin-18,
pubmed-meshheading:17237446-Mice,
pubmed-meshheading:17237446-Mice, Knockout,
pubmed-meshheading:17237446-Peptide Hydrolases,
pubmed-meshheading:17237446-Pulmonary Emphysema,
pubmed-meshheading:17237446-Receptors, Interleukin-18,
pubmed-meshheading:17237446-Smoke,
pubmed-meshheading:17237446-Tobacco
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pubmed:year |
2007
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pubmed:articleTitle |
IL-18 is induced and IL-18 receptor alpha plays a critical role in the pathogenesis of cigarette smoke-induced pulmonary emphysema and inflammation.
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pubmed:affiliation |
Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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