Activation of p38 MAPK Pathway by Hepatitis C Virus E2 in Cells Transiently Expressing DC-SIGN
Activation of p38 MAPK Pathway by Hepatitis C Virus E2 in Cells Transiently Expressing DC-SIGN
复制标题
丙型肝炎病毒 E2 在瞬时表达 DC-SIGN 的细胞中激活 p38 MAPK 通路
DOI：
10.1007/s12013-009-9069-0
复制
发表时间：
2010-01-01
影响因子：
2.6
通讯作者：
Qi, Zhong-Tian
中科院分区：
文献类型：
--
作者：
Chen, Qiu-Li;Zhu, Shi-Ying;Qi, Zhong-Tian
树突状细胞特异性细胞间粘附分子3-抓取非整合素（DC-SIGN）是丙型肝炎病毒的细胞受体，用于结合病毒包膜糖蛋白E2。DC-SIGN与E2的相互作用可能引起与病毒发病机制有关的细胞信号转导。我们建立了DC-SIGN瞬时转染的细胞模型来研究p38丝裂原活化蛋白激酶（MAPK）信号通路对E2处理的反应。HEK 293 T和HeLa是DC-SIGN缺陷型细胞系。在转染DC-SIGN的HEK 293 T和HeLa细胞表面均可检测到DC-SIGN，并且与HeLa细胞相比，转染的HEK 293 T细胞中DC-SIGN的水平更高。转染的HEK 293 T细胞具有E2结合能力。在转染的HEK 293 T中，p38 MAPK磷酸化水平在E2处理后增加，并且在用针对DC-SIGN的抗体阻断DC-SIGN后降低。下游转录因子激活转录因子（ATF）-2的磷酸化也被E2通过DC-SIGN上调。用稳定表达DC-SIGN的NIH 3 T3细胞和Huh 7细胞获得了类似的结果。我们的结果表明，HEK 293 T中DC-SIGN的瞬时表达是研究E2触发的p38 MAPK途径的有用细胞模型，这可能为了解细胞受体介导的信号事件和病毒发病机制提供信息。
Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is a cellular receptor for hepatitis C virus for the binding of viral envelope glycoprotein E2. Interaction of DC-SIGN with the E2 may evoke cellular signal transduction implicated in viral pathogenesis. We developed a cell model with DC-SIGN transient transfection to study p38 mitogen-activated protein kinase (MAPK) signaling pathway in response to the E2 treatment. HEK293T and HeLa were DC-SIGN-deficient cell lines. DC-SIGN was detectable at the surface of HEK293T and HeLa transfected with DC-SIGN, and the levels of DC-SIGN were high in transfected-HEK293T as compared with HeLa. The transfected-HEK293T displayed ability for the E2 binding. In the transfected-HEK293T, level of p38 MAPK phosphorylation was increased upon the E2 treatment and reduced following blockage of DC-SIGN with an antibody against DC-SIGN. Phosphorylation of downstream transcription factor activating transcription factor (ATF)-2 was also up-regulated by the E2 via DC-SIGN. Similar results were obtained with NIH3T3 cells stably expressing DC-SIGN and Huh7 cells. Our results indicate that DC-SIGN transient expression in HEK293T is a useful cell model for investigating p38 MAPK pathway triggered by the E2, which may provide information for understanding cellular receptors-mediated signaling events and the viral pathogenesis.