論文 - 詳細
| RRC ID | 43174 |
|---|---|
| 著者 | Murao K, Imachi H, Yu X, Cao WM, Nishiuchi T, Chen K, Li J, Ahmed RA, Wong NC, Ishida T. |
| タイトル | Interferon alpha decreases expression of human scavenger receptor class BI, a possible HCV receptor in hepatocytes. |
| ジャーナル | Gut |
| 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 alpha (IFN alpha)-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 IFN alpha 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 IFN alpha. Decreased hSR-BI/CLA-1 expression in IFN alpha-treated cells was due to lower transcriptional activity of the promoter. A potential pathway for the effect of IFN alpha 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 IFN alpha elicited a rapid phosphorylation of STAT1/STAT2, a known target of IFN alpha signalling. In addition, the mutagenesis of a STAT1/STAT2 response element in the hSR-BI/CLA-1 promoter abolished the ability of IFN alpha to suppress promoter activity. CONCLUSIONS:Together, these results indicate that the STAT1/STAT2 pathway participates in IFN alpha inhibition 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. |
| 巻・号 | 57(5) |
| ページ | 664-71 |
| 公開日 | 2008-5-1 |
| DOI | 10.1136/gut.2006.111443 |
| PII | gut.2006.111443 |
| PMID | 17998316 |
| MeSH | Antigens, CD / metabolism Antiviral Agents / pharmacology* Blotting, Western Cells, Cultured DNA, Viral / metabolism Female Gene Expression Regulation / physiology Hepacivirus / metabolism* Hepatitis C / drug therapy Hepatitis C / metabolism* Hepatocytes / metabolism Hepatocytes / virology Humans Interferon-alpha / pharmacology* Male RNA, Viral / metabolism Receptors, Virus / antagonists & inhibitors* Reverse Transcriptase Polymerase Chain Reaction Scavenger Receptors, Class B / antagonists & inhibitors* Scavenger Receptors, Class B / metabolism Tetraspanin 28 Viral Proteins / drug effects Virus Replication / drug effects |
| IF | 19.819 |
| 引用数 | 23 |
| WOS 分野 | GASTROENTEROLOGY & HEPATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2 HuH-7(RCB1366) |