title: Involvement of p38 signaling pathway in interferon-alpha-mediated antiviral activity toward hepatitis C virus.
abstract: We studied the involvement of the p38 signaling pathway in the interferon (IFN)-alpha-mediated antiviral activity toward hepatitis C virus (HCV) using HCV subgenomic replicon cells. When the cells were treated with IFN-alpha in the presence of p38 inhibitor, the suppressive effect of IFN-alpha on replicon RNA was reduced. Inhibition of p38 had almost no influence on phosphorylation of signal transducer and activator transcription factor 1 (STAT1) and interferon stimulatory response element-dependent gene expression after IFN-alpha treatment. This indicates that the anti-HCV activity through p38 may be independent of the Janus kinase-STAT pathway. Treatment with the inhibitor of the mitogen-activated protein kinase-activated protein kinase 2 (MK2) showed the same level of reduction in the IFN-alpha-mediated anti-HCV activity as that with the p38 inhibitor. Thus, MK2 may also be responsible for the anti-HCV activity through p38. In conclusion, the p38-MK2 signaling pathway may be substantially involved in the IFN-alpha-mediated anti-HCV activity.
authors.affiliation: Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ishida
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ohkawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hosui
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiramatsu
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kanto
authors.forename: Keiji
authors.initials: K
authors.lastname: Ueda
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D053613:Janus Kinase 1; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D012093:Replicon; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D016898:Interferon-alpha; D012367:RNA, Viral; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases