DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jeong, Won-il | ko |
dc.contributor.author | Park, Ogyi | ko |
dc.contributor.author | Gao, Bin | ko |
dc.date.accessioned | 2010-04-14T02:11:29Z | - |
dc.date.available | 2010-04-14T02:11:29Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 2008-01 | - |
dc.identifier.citation | GASTROENTEROLOGY, v.134, no.1, pp.248 - 258 | - |
dc.identifier.issn | 0016-5085 | - |
dc.identifier.uri | http://hdl.handle.net/10203/17691 | - |
dc.description.abstract | Background & Aims: chronic alcohol drinking accelerates liver fibrosis in patients with viral hepatitis that cannot be fully explained by ethanol-enhanced liver damage. Here, we identified a novel mechanism by which alcohol accelerates liver fibrosis: inhibition of the antifibrotic effects of natural killer (NK) cells and interferon-gamma (IFN-gamma). Methods: Alcohol administration was achieved by feeding mice with a liquid diet containing 5% ethanol for 8 weeks. Liver fibrosis was induced by administration of carbon tetrachloride (CCl4) for 2 weeks. Hepatic stellate cells (HSCs) were also isolated and cultured for in vitro studies. Results: CCl4 treatment induced greater fibrosis and less apoptosis of HSCs in ethanol-fed mice compared with pair-fed mice. Polyinosinic-polycytidylic acid (Poly I:C) or IFN-gamma treatment inhibited liver fibrosis in pair-fed but not in ethanol-fed mice. Poly I:C activation of NK cell cytotoxicity against HSCs was attenuated in ethanol-fed mice compared with pair-fed mice, which was due to reduced natural killer group 2 member D (NKG2D), tumor necrosis factor-related apoptosis-inducing ligand, and IFN-gamma expression on NK cells from ethanol-fed mice. In vitro, HSCs from ethanol-fed mice were resistant to IFN-gamma-induced cell cycle arrest and apoptosis compared with pair-fed mice. Such resistance was due to diminished IFN-gamma activation of signal transducer and activator of transcription 1 (STAT1) in HSCs from ethanol-fed mice caused by the induction of suppressors of cytokine signaling proteins and the production of oxidative stress. Finally, HSCs from ethanol-fed mice were resistant to NK cell killing, which can be reversed by transforming growth factor-beta 1 (TGF-beta 1) neutralizing antibody. Conclusions: Chronic ethanol consumption attenuates the antifibrotic effects of NK/IFN-gamma/STAT1 in the liver, representing new and different therapeutic targets with which to treat alcoholic liver fibrosis. | - |
dc.description.sponsorship | Supported by the intramural program of National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health. | en |
dc.language | English | - |
dc.language.iso | en_US | en |
dc.publisher | W B SAUNDERS CO-ELSEVIER INC | - |
dc.subject | HEPATIC STELLATE CELLS | - |
dc.subject | NECROSIS-FACTOR-ALPHA | - |
dc.subject | POLY I-C | - |
dc.subject | INTERFERON-GAMMA | - |
dc.subject | ACUTE ETHANOL | - |
dc.subject | NK CELLS | - |
dc.subject | ACTIVATION | - |
dc.subject | RAT | - |
dc.subject | MECHANISMS | - |
dc.subject | INHIBITION | - |
dc.title | Abrogation of the antifibrotic effects of natural killer cells/interferon-gamma contributes to alcohol acceleration of liver fibrosis | - |
dc.type | Article | - |
dc.identifier.wosid | 000252066400031 | - |
dc.identifier.scopusid | 2-s2.0-37349108815 | - |
dc.type.rims | ART | - |
dc.citation.volume | 134 | - |
dc.citation.issue | 1 | - |
dc.citation.beginningpage | 248 | - |
dc.citation.endingpage | 258 | - |
dc.citation.publicationname | GASTROENTEROLOGY | - |
dc.identifier.doi | 10.1053/j.gastro.2007.09.034 | - |
dc.embargo.liftdate | 9999-12-31 | - |
dc.embargo.terms | 9999-12-31 | - |
dc.contributor.localauthor | Jeong, Won-il | - |
dc.contributor.nonIdAuthor | Park, Ogyi | - |
dc.contributor.nonIdAuthor | Gao, Bin | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | HEPATIC STELLATE CELLS | - |
dc.subject.keywordPlus | NECROSIS-FACTOR-ALPHA | - |
dc.subject.keywordPlus | POLY I-C | - |
dc.subject.keywordPlus | INTERFERON-GAMMA | - |
dc.subject.keywordPlus | ACUTE ETHANOL | - |
dc.subject.keywordPlus | NK CELLS | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | RAT | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | INHIBITION | - |
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