國家衛生研究院 NHRI:Item 3990099045/2193
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    题名: IL-4 suppresses the expression and the replication of hepatitis B virus in the hepatocellular carcinoma cell line Hep3B
    作者: Lin, SJ;Shu, PY;Chang, CM;Ng, AK;Hu, CP
    贡献者: Division of Molecular and Genomic Medicine
    摘要: IL-4 has been known as a Th2 cytokine and can act on B cells, T cells, and monocytes. In this study we demonstrate that IL-4Rs are expressed on human hepatocellular carcinoma (HCC) cells. We found that IL-4 suppresses hepatitis B surface Ag (HBsAg) mRNA and HBsAg production in the Hep3B cell line, which contains an integrated hepatitis B virus (HBV) genome and constitutively secretes HBsAg. When Hep3B cells are further transfected with the plasmid pHBV3.6 that contains > 1 U of HBV genome, IL-4 could suppress the production of all HBV RNA and secreted HBsAg and hepatitis B virus e Ag. Furthermore, an endogenous DNA polymerase activity assay shows a decrease in HBV DNA after IL-4 treatment. Using luciferase reporter assays we have demonstrated that IL-4 could suppress the activity of the surface promoter II and the core promotor (CP). To delineate how IL-4 suppressed the transcription of HBV genes, we have examined the effect of IL-4 on the expression of transcription factors that are known to bind to the core upstream regulatory sequence, which colocalizes with enhancer II of the HBV genome. Our results demonstrate that IL-4 suppresses the expression of C/EBPalpha. Furthermore, overexpression of C/EBPalpha blocked 43 and 30% of the IL-4-mediated suppression of CP activity and IL-4-induced suppression of pregenomic RNA, respectively. Finally, we have demonstrated that mutations affecting the C/EBPalpha-binding sites on core upstream regulatory sequence/enhancer 11 completely abolish the IL-4-mediated suppression of CP activity. Thus, down-regulation of C/EBPa may be involved in the anti-HBV effect of IL-4 in Hep3B cells.
    关键词: Immunology
    日期: 2003-11-01
    關聯: Journal of Immunology. 2003 Nov;171(9):4708-4716.
    Link to: http://www.jimmunol.org/cgi/content/abstract/171/9/4708
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-1767&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000186136800028
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0142211126
    显示于类别:[張仲明] 期刊論文

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