Ishida Hisashi, Ohkawa Kazuyoshi, Hosui Atsushi, Hiramatsu Naoki, Kanto Tatsuya, Ueda Keiji, Takehara Tetsuo, Hayashi Norio
Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
Biochem Biophys Res Commun. 2004 Aug 27;321(3):722-7. doi: 10.1016/j.bbrc.2004.07.015.
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.
我们使用丙型肝炎病毒（HCV）亚基因组复制子细胞研究了p38信号通路在干扰素（IFN）-α介导的抗HCV病毒活性中的作用。当细胞在p38抑制剂存在的情况下用IFN-α处理时，IFN-α对复制子RNA的抑制作用减弱。抑制p38对IFN-α处理后信号转导和转录激活因子1（STAT1）的磷酸化以及干扰素刺激反应元件依赖性基因表达几乎没有影响。这表明通过p38的抗HCV活性可能独立于Janus激酶-STAT途径。用丝裂原活化蛋白激酶激活的蛋白激酶2（MK2）抑制剂处理显示，IFN-α介导的抗HCV活性降低水平与p38抑制剂相同。因此，MK2也可能通过p38参与抗HCV活性。总之，p38-MK2信号通路可能在很大程度上参与IFN-α介导的抗HCV活性。
