title: Interferon alpha and ribavirin collaboratively regulate p38 mitogen-activated protein kinase signaling in hepatoma cells.
abstract: Signaling events triggered by interferon alpha (IFN-α) and ribavirin are involved in anti-hepatitis C virus (HCV) action. The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in HCV pathogenesis. Effects of IFN-α and ribavirin on p38 MAPK signaling were investigated in human hepatoma cells. Type I IFN receptor 2 (IFNAR2) mediated IFN-α-induced p38 MAPK phosphorylation. Also, p38 MAPK phosphorylation was enhanced by ribavirin. Treatment for 48 h with a combination of IFN-α and ribavirin increased p38 MAPK phosphorylation, whereas the treatment for 72 h reduced p38 MAPK phosphorylation. Cell culture-derived HCV (HCVcc) infection dramatically increased p38 MAPK phosphorylation and such phosphorylation was inhibited by IFN-α or ribavirin. Moreover, siRNA-mediated knockdown of p38 MAPK resulted in enhancement of ribavirin-dependent HCV RNA replication. These results suggest that regulation of p38 MAPK signaling by IFN-α and ribavirin might contribute to anti-HCV action.
authors: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, China.
authors: Sheng-Fei
authors: SF
authors: He
authors: Wen
authors: W
authors: Wang
authors: Hao
authors: H
authors: Ren
authors: Lan-Juan
authors: LJ
authors: Zhao
authors: Zhong-Tian
authors: ZT
authors: Qi
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000201:enzymology*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D016174:Hepacivirus / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000378:metabolism; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C507964:IFNAR1 protein, human; D016898:Interferon-alpha; D034741:RNA, Small Interfering; D053633:Receptor, Interferon alpha-beta; D012254:Ribavirin; D048051:p38 Mitogen-Activated Protein Kinases