Type I IFN induced IL1-Ra expression in hepatocytes is mediated by activating STAT6 through the formation of STAT2 : STAT6 heterodimer

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题名:	Type I IFN induced IL1-Ra expression in hepatocytes is mediated by activating STAT6 through the formation of STAT2 : STAT6 heterodimer
作者:	Wan, L (Wan, Lei);Lin, CW (Lin, Cheng-Wen);Lin, YJ (Lin, Ying-Ju);Sheu, JJC (Sheu, Jim J. C.);Chen, BH (Chen, Bing-Hung);Liao, CC (Liao, Chiu-Chu);Tsai, Y (Tsai, Yuhsin);Lin, WY (Lin, Wei-Yong);Lai, CH (Lai, Chih-Ho);Tsai, FJ (Tsai, Fuu Jen)
贡献者:	Department of Bioinformatics
关键词:	type I interferon;STAT6;STAT2;IL-1Ra;INTERLEUKIN-1 RECEPTOR ANTAGONIST;CHRONIC HEPATITIS-C;BLOOD MONONUCLEAR-CELLS;INTERFERON-ALPHA;SIGNAL-TRANSDUCTION;GENE-EXPRESSION;ANTIVIRAL STATE;TH1/TH2 BALANCE;TARGET GENES;PATHWAY
日期:	2008-06
上传时间:	2010-03-26 02:56:39 (UTC+0)
出版者:	Asia University
摘要:	The biological activities of type I interferons (IFNs) are mediated by their binding to a heterodimer receptor complex (IFNAR1 and IFNAR2), resulting in the activation of the JAK (JAK1 and TYK2)-STAT (1, 2, 3, 5 isotypes) signalling pathway. Although several studies have indicated that IFN-alpha and IFN-beta can activate complexes containing STAT6, the biological role of this activation is still unknown. We found that exposure of hepatoma cells (HuH7 and Hep3B) to IFN-alpha or IFN-beta led to the activation of STAT6. Activated STAT6 in turn induced the formation of STAT2: STAT6 complexes, which led to the secretion of IL-1Ra. The activation of STAT6 by type I IFN in hepatocytes was mediated by JAK1 and Tyk2. In addition, IFN-alpha or IFN-beta significantly enhanced the stimulatory effect of IL-1 beta on production of IL-1Ra. The present study suggests a novel function of IFN-alpha and IFN-beta signalling in human hepatocytes. Our results provide evidence for the mechanism how IFN-alpha and IFN-beta modulate inflammatory responses through activation of STAT6 and production of secreted IL-1Ra.
關聯:	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 12 (3): 876-888
显示于类别:	[生物資訊與醫學工程學系 ] 期刊論文

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