國家衛生研究院 NHRI:Item 3990099045/9321
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    题名: Ifit1 protects against lipopolysaccharide and D-galactosamine-induced fatal hepatitis by inhibiting activation of the JNK pathway
    作者: Chang, A;Chen, Y;Shen, W;Gao, R;Zhou, W;Yang, S;Liu, Y;Luo, Y;Chuang, TH;Sun, P;Liu, C;Xiang, R
    贡献者: Immunology Research Center
    摘要: Treatment of mice with lipopolysaccharide (LPS) and the liver-specific transcriptional inhibitor D-(+)-galactosamine (GalN) induces fatal hepatitis, which is mediated by tumor necrosis factor alpha (TNF-alpha) and characterized by massive hepatic apoptosis. Previous studies suggest that GalN increases the sensitivity to LPS/TNF-alpha, probably by blocking the transcription of protective factors, but the identity of most of these factors is still unclear. Here, we report that Ifit1 protects against LPS/GalN-induced fatal hepatitis. Forced expression of Ifit1 in hepatocytes significantly diminished TNF-alpha-mediated apoptosis. Moreover, targeted expression of Ifit1 in the liver by recombinant adeno-associated virus serotype 8 protected mice from LPS/GalN-induced lethal hepatitis, which was associated with the inhibition of TNF-alpha-mediated activation of the c-Jun N-terminal kinase (JNK)-Bim cascade. Furthermore, Ifit1 bound to a scaffolding protein Axin and inhibited its function to mediate JNK activation. Together, our data demonstrate that Ifit1 is a novel protective factor that inhibits LPS/GalN-induced (TNF-alpha-mediated) fatal hepatitis, suggesting that Ifit1 is a potential therapeutic target for treatment of inflammatory liver diseases.
    日期: 2015-11
    關聯: Journal of Infectious Diseases. 2015 Nov 1;212(9):1509-1520.
    Link to: http://dx.doi.org/10.1093/infdis/jiv221
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-1899&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000364767500020
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84946136617
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