FasL/Fas Pathway Is Involved in Dengue Virus Induced Apoptosis of the Vascular Endothelial Cells

FasL/Fas Pathway Is Involved in Dengue Virus Induced Apoptosis of the Vascular Endothelial Cells
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FasL/Fas 通路参与登革热病毒诱导的血管内皮细胞凋亡

DOI:
10.1002/jmv.21815
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发表时间:
2010-08-01
影响因子:
12.7
通讯作者:
Huang, Junqi
Huang, Junqi
中科院分区:
医学3区
文献类型:
--
作者:
Liao, Hongwu;Xu, Juan;Huang, Junqi

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The hallmark of the dengue hemorrhagic fever/dengue shock syndrome is hematologic abnormality. The pathogenesis of dengue hemorrhagic fever/dengue shock syndrome remains unknown. Our work showed that the dengue virus serotype-2 induced apoptosis in human umbilical vein endothelial cells. Fas (CD95), Tumor Necrosis Factor receptors, and Tumor Necrosis Factor-related apoptosis-inducing ligand receptors are the most common death receptors, which can induce apoptosis. Compared with the untreated human umbilical vein endothelial cells, Fas expression was increased both in the mRNA level and on the surface of infected human umbilical vein endothelial cells. FasL was expressed at similar levels on human umbilical vein endothelial cells over a course of dengue virus serotype-2 infection, but the expression in mRNA level was increased in infected human umbilical vein endothelial cells. It is possible that there is soluble FasL secreted from human umbilical vein endothelial cells in the supernatant. Tumor Necrosis Factor-related apoptosis-inducing ligand receptor 1 and Tumor Necrosis Factor receptors 1-2 were constantly very low, whereas Tumor Necrosis Factor-related apoptosis-inducing ligand receptors 2-4 decreased after dengue virus serotype-2 infection. This result suggested that dengue virus serotype-2 may inhibit Tumor Necrosis Factor-related apoptosis-inducing ligand receptors-induced apoptosis. The apoptotic rates in human umbilical vein endothelial cells were decreased upon the addition of caspase family inhibitors. In addition, activated caspase 8 and caspase 3 were also observed by Western blot following dengue virus serotype-2 infection. Thus, it is shown that the Fas/FasL pathway may participate in dengue virus-induced apoptosis of vascular endothelial cells in vitro. J. Med. Virol. 82:1392-1399, 2010. (C) 2010 Wiley-Liss, Inc.