Source:http://linkedlifedata.com/resource/pubmed/id/16410367
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2006-5-11
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pubmed:abstractText |
Hepatic ischemia occurs in the settings of trauma, transplantation, and elective liver resections. The initiating events that account for local organ damage are only partially understood. Interferon (IFN) regulatory factor-1 (IRF-1) is a transcription factor that regulates the expression of a number of genes involved in both innate and acquired immunity; however, its function in liver injury is unknown. Therefore, the purpose of this study was to investigate the role of IRF-1 in hepatic ischemia-reperfusion (I/R) injury. In C57BL/6 mice undergoing 60 min of hepatic ischemia, IRF-1 protein expression increased as early as 1 h after reperfusion. IRF-1 knockout mice were significantly protected from hepatic I/R-induced damage compared with their wild-type controls. Hepatic I/R injury resulted in marked activation of the MAP kinase c-Jun NH(2)-terminal kinase (JNK) in wild-type mice but not IRF-1 knockout mice. IRF-1 knockout mice also exhibited significantly lower hepatic expression of TNF-alpha, IL-6, ICAM-1, and inducible nitric oxide synthase (iNOS) mRNA. Adenoviral delivery of IRF-1 into C57BL/6 mice resulted in increased liver damage even without an ischemic insult. This injury was associated with increased JNK activation and hepatic iNOS expression. Because IRF-1 contributed to liver injury, we also examined for inflammatory signals that regulated IRF-1 gene expression in cultured hepatocytes. Whereas IFN-gamma and IFN-beta were strong inducers of IRF-1 mRNA (>10-fold) in a time- and dose-dependent manner, TNF-alpha and IL-1beta also induced IRF-1 mRNA to a lesser extent (2- to 3-fold). IL-6 and lipopolysaccharide had no effect on IRF-1 expression. This study demonstrates that IRF-1 exerts a harmful role in hepatic I/R injury by modulating the expression of multiple inflammatory mediators. We further show that IRF-1-mediated injury involves the activation of JNK and that hepatocellular IRF-1 expression itself is regulated by specific cytokines.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0193-1857
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pubmed:author |
pubmed-author:ChanMeagan HMH,
pubmed-author:CritchlowNathan DND,
pubmed-author:GellerDavid ADA,
pubmed-author:IkedaAtsushiA,
pubmed-author:IzuishiKunihikoK,
pubmed-author:JeyabalanGeethaG,
pubmed-author:NakaoAtsunoriA,
pubmed-author:StangMichael TMT,
pubmed-author:TsungAllanA,
pubmed-author:YimJohn HJH
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pubmed:issnType |
Print
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pubmed:volume |
290
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
G1261-8
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pubmed:meshHeading |
pubmed-meshheading:16410367-Animals,
pubmed-meshheading:16410367-Liver,
pubmed-meshheading:16410367-Male,
pubmed-meshheading:16410367-Mice,
pubmed-meshheading:16410367-Mice, Inbred C57BL,
pubmed-meshheading:16410367-Mice, Knockout,
pubmed-meshheading:16410367-Rats,
pubmed-meshheading:16410367-Rats, Sprague-Dawley,
pubmed-meshheading:16410367-Reperfusion Injury,
pubmed-meshheading:16410367-Transcription Factors
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pubmed:year |
2006
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pubmed:articleTitle |
The transcription factor interferon regulatory factor-1 mediates liver damage during ischemia-reperfusion injury.
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pubmed:affiliation |
Department of Surgery, University of Pittsburgh, PA 15213, USA.
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pubmed:publicationType |
Journal Article
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