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Interferon α decreases expression of human scavenger receptor class BI, a possible HCV receptor in hepatocytes
  1. K Murao1,
  2. H Imachi1,
  3. X Yu1,
  4. W M Cao1,
  5. T Nishiuchi1,
  6. K Chen1,
  7. J Li1,
  8. R A M Ahmed1,
  9. N C W Wong2,
  10. T Ishida1
  1. 1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa, Japan
  2. 2 Departments of Medicine and Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, Health Sciences Center, Alberta, Canada
  1. Dr K Murao, Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan; mkoji{at}kms.ac.jp

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 a more deadly consequence is hepatocellular carcinoma. Interferon α (IFNα)-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 current interest in the potential role of IFNα in hSR-BI/CLA-1 expression in HepG2 cells.

Results: It was shown that endogenous hepatocyte expression of hSR-BI/CLA-1 was suppressed by exposure to IFNα. Decreased hSR-BI/CLA-1 expression in IFNα-treated cells was due to lower transcriptional activity of the promoter. A potential pathway for the effect of IFNα on hSR-BI/CLA-1 promoter activity was identified when the inhibitory action of IFN was abrogated in signal transducer and activator of transcription 1 (STAT1)/STAT2 knocked-down cells. Exposure of HepG2 cells to IFNα elicited a rapid phosphorylation of STAT1/STAT2, a known target of IFNα signalling. In addition, the mutagenesis of a STAT1/STAT2 response element in the hSR-BI/CLA-1 promoter abolished the ability of IFNα to suppress promoter activity.

Conclusions: Together, these results indicate that the STAT1/STAT2 pathway participates in IFNα 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.

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  • Competing interests: None.

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