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Interferon-α decreases expression of human scavenger receptor class BI, possible HCV receptor in hepatocytes.
  1. Koji Murao (mkoji{at}kms.ac.jp)
  1. Kagawa University, Japan
    1. Hitomi Imachi (ihitomi{at}kms.ac.jp)
    1. Kagawa University, Japan
      1. Xiao Yu (shelley_yxsz{at}sina.com)
      1. Kagawa University, Japan
        1. Wen M Cao (cao1008{at}hotmail.com)
        1. Kagawa University, Japan
          1. Takamasa Nishiuchi (t111nishiuchi{at}yahoo.co.jp)
          1. Kagawa University, Japan
            1. Ke Chen (ness12cc{at}msn.com)
            1. Kagawa University, Japan
              1. Junhua Li (lijh606{at}yahoo.co.jp)
              1. Kagawa University, Japan
                1. Rania AM Ahmed (rania3a{at}kms.ac.jp)
                1. Kagawa University, Japan
                  1. Norman CW Wong (ncwwong{at}ucalgary.ca)
                  1. Faculty of Medicine, University of Calgary, Canada
                    1. Toshihiko Ishida (tishida{at}kms.ac.jp)
                    1. Kagawa University, Japan

                      Abstract

                      Background: Infection with the hepatitis C virus (HCV) causes acute hepatitis. This disease has a high probability of becoming chronic and leading to cirrhosis but more deadly consequence is hepatocellular carcinoma. Interferon (IFN)-?-based treatment combined with ribavirin is the major therapeutic choice available for the treatment of chronic HCV infection. Aims: The scavenger receptor class B type I (SR-BI) or its human homologue CD36 and LIMPII Analogous-1 (hSR-BI/CLA-1) has recently been shown to interact with HCV envelope glycoprotein E2, thus suggesting that it might participate in entry of the virus into host cells. This rationale underlies our interest of the potential role of IFN-? on hSR-BI/CLA-1 expression in HepG2 cells. Results: Results showed that endogenous hepatocytes expression of hSR-BI/CLA-1 was suppressed by exposure to IFN-?. Decreased hSR-BI/CLA-1 expression in IFN-? treated cells was due to lower transcriptional activity of the promoter. A potential pathway for the effect of IFN-? on hSR-BI/CLA-1 promoter activity was identified when the inhibitory action of interferon was abrogated in STAT1/STAT2 knocked down cells. Exposure of HepG2 cells to IFN-? elicited a rapid phosphorylation of STAT1/STAT2, a known target of IFN-? signaling. In addition, the mutagenesis of a STAT1/STAT2 response element in the hSR-BI/CLA-1 promoter abolished the ability of IFN-? to suppress promoter activity. Conclusions: Together, these results indicate that the STAT1/STAT2 pathway participates in IFN-?-inhibtion of hSR-BI/CLA-1 expression and raise the possibility that lowering the expression of this gene may be of therapeutic value for treating HCV infections.

                      • HCV
                      • HDL
                      • STAT
                      • interferon
                      • receptor

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