B7-H4 reverse signaling induces the apoptosis of EBV-transformed B cells through Fas ligand up-regulation
B7-H4 reverse signaling induces the apoptosis of EBV-transformed B cells through Fas ligand up-regulation
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DOI：
10.1016/j.canlet.2008.02.067
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发表时间：
2008-08-08
期刊：
影响因子：
9.7
通讯作者：
Hur, Dae Young
中科院分区：
文献类型：
--
作者：
Song, Hyunkeun;Park, Gabin;Hur, Dae Young
B7-H4通过下调T细胞介导的免疫而对免疫应答具有抑制作用，但是B7-H4分子与反分子的结合如何影响表达B7-H4的细胞的信号传导机制尚不清楚。在这项研究中，我们发现，B7-H4的表达增强的B细胞感染EB病毒（EBV）和这些分子的触发诱导EBV转化的B细胞凋亡。B7-H4的参与首先增加细胞内ROS水平，然后诱导FasL的表达。B7-H4的参与随后引起与细胞色素e和AIF相关的Fas介导的和半胱天冬酶依赖的细胞凋亡，并且在EBV转化的B细胞上从线粒体释放EndoG。这些结果提示B7-H4可能是治疗EBV相关恶性疾病的潜在靶点。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
B7-H4 has an inhibitory effect on immune responses via the down-regulation of T cell-mediated immunity, but how the engagement of B7-H4 molecules by counter molecules affects the signaling mechanism of the B7-H4-expressing cells is poorly defined. In this study, we found that B7-H4 expression was enhanced on B cells infected with Epstein-Barr virus (EBV) and that triggering of these molecules induced apoptosis of EBV-transformed B cells. Engagement of B7-H4 initially increased intracellular level of ROS, which then induced the expression of FasL. Engagement of B7-H4 subsequently provoked Fas-mediated and caspase-dependent apoptosis in association with cytochrome e and AIF, and EndoG was released from the mitochondria on EBV-transformed B cells. These results suggest that B7-H4 may be a potential therapeutic target for EBV involved malignancy diseases. (C) 2008 Elsevier Ireland Ltd. All rights reserved.