| pubmed-article:16410367 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16410367 | lifeskim:mentions | umls-concept:C0035126 | lld:lifeskim |
| pubmed-article:16410367 | lifeskim:mentions | umls-concept:C0040648 | lld:lifeskim |
| pubmed-article:16410367 | lifeskim:mentions | umls-concept:C0063700 | lld:lifeskim |
| pubmed-article:16410367 | lifeskim:mentions | umls-concept:C0151763 | lld:lifeskim |
| pubmed-article:16410367 | lifeskim:mentions | umls-concept:C0086597 | lld:lifeskim |
| pubmed-article:16410367 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:16410367 | pubmed:dateCreated | 2006-5-11 | lld:pubmed |
| pubmed-article:16410367 | 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. | lld:pubmed |
| pubmed-article:16410367 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16410367 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16410367 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:16410367 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16410367 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16410367 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:16410367 | pubmed:issn | 0193-1857 | lld:pubmed |
| pubmed-article:16410367 | pubmed:author | pubmed-author:GellerDavid... | lld:pubmed |
| pubmed-article:16410367 | pubmed:author | pubmed-author:IzuishiKunihi... | lld:pubmed |
| pubmed-article:16410367 | pubmed:author | pubmed-author:IkedaAtsushiA | lld:pubmed |
| pubmed-article:16410367 | pubmed:author | pubmed-author:NakaoAtsunori... | lld:pubmed |
| pubmed-article:16410367 | pubmed:author | pubmed-author:YimJohn HJH | lld:pubmed |
| pubmed-article:16410367 | pubmed:author | pubmed-author:TsungAllanA | lld:pubmed |
| pubmed-article:16410367 | pubmed:author | pubmed-author:StangMichael... | lld:pubmed |
| pubmed-article:16410367 | pubmed:author | pubmed-author:JeyabalanGeet... | lld:pubmed |
| pubmed-article:16410367 | pubmed:author | pubmed-author:CritchlowNath... | lld:pubmed |
| pubmed-article:16410367 | pubmed:author | pubmed-author:ChanMeagan... | lld:pubmed |
| pubmed-article:16410367 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16410367 | pubmed:volume | 290 | lld:pubmed |
| pubmed-article:16410367 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16410367 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16410367 | pubmed:pagination | G1261-8 | lld:pubmed |
| pubmed-article:16410367 | pubmed:meshHeading | pubmed-meshheading:16410367... | lld:pubmed |
| pubmed-article:16410367 | pubmed:meshHeading | pubmed-meshheading:16410367... | lld:pubmed |
| pubmed-article:16410367 | pubmed:meshHeading | pubmed-meshheading:16410367... | lld:pubmed |
| pubmed-article:16410367 | pubmed:meshHeading | pubmed-meshheading:16410367... | lld:pubmed |
| pubmed-article:16410367 | pubmed:meshHeading | pubmed-meshheading:16410367... | lld:pubmed |
| pubmed-article:16410367 | pubmed:meshHeading | pubmed-meshheading:16410367... | lld:pubmed |
| pubmed-article:16410367 | pubmed:meshHeading | pubmed-meshheading:16410367... | lld:pubmed |
| pubmed-article:16410367 | pubmed:meshHeading | pubmed-meshheading:16410367... | lld:pubmed |
| pubmed-article:16410367 | pubmed:meshHeading | pubmed-meshheading:16410367... | lld:pubmed |
| pubmed-article:16410367 | pubmed:meshHeading | pubmed-meshheading:16410367... | lld:pubmed |
| pubmed-article:16410367 | pubmed:year | 2006 | lld:pubmed |
| pubmed-article:16410367 | pubmed:articleTitle | The transcription factor interferon regulatory factor-1 mediates liver damage during ischemia-reperfusion injury. | lld:pubmed |
| pubmed-article:16410367 | pubmed:affiliation | Department of Surgery, University of Pittsburgh, PA 15213, USA. | lld:pubmed |
| pubmed-article:16410367 | pubmed:publicationType | Journal Article | lld:pubmed |
| entrez-gene:16362 | entrezgene:pubmed | pubmed-article:16410367 | lld:entrezgene |
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