Herpesvirus entry mediator (HVEM) attenuates signals mediated by the lymphotoxin β receptor (LTβR) in human cells stimulated by the shared ligand LIGHT.
Herpesvirus entry mediator (HVEM) attenuates signals mediated by the lymphotoxin β receptor (LTβR) in human cells stimulated by the shared ligand LIGHT.
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DOI：
10.1016/j.molimm.2014.06.013
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发表时间：
2014-11
影响因子：
3.6
通讯作者：
Muller WJ
中科院分区：
文献类型：
--
作者：
Bechill J;Muller WJ
由肿瘤坏死因子受体超家族成员介导的信号调节多种过程的网络，包括炎症反应的启动和在有利于存活和死亡的途径之间改变细胞命运。尽管TNF-α受体的这种信号通路已经得到了很好的描述，但关于TNF超家族成员LIGHT诱导的信号传导以及LIGHT的两种受体LTβR和HVEM在同一细胞中的表达是如何不同地改变信号传导的，我们使用HVEM和LTβR相对表达不同的细胞系来证明由这些受体介导的LIGHT诱导的信号传导与TRAF 2稳定性的改变和RelA核转位有关。炎症趋化因子CXCL 10的产生主要由LTβR介导。HVEM的高表达与细胞存活相关，而无对抗性的LTβR信号通路有利于导致凋亡的途径。重要的是，在具有低内源性表达的细胞中恢复HVEM表达重现了具有较高内源性表达的细胞的表型。总之，我们的数据提供了HVEM和LTβR的相对表达调节LIGHT刺激的典型NF-κB和促凋亡信号的证据。
Signals mediated by members of the tumor necrosis factorreceptor superfamily modulate a network of diverse processes including initiation of inflammatory responses and altering cell fate between pathways favoring survival and death. Although such pathways have been well-described for the TNF-αreceptor, less is known about signalinginduced by the TNF superfamily member LIGHT and how it is differentially altered by expression of its two receptors LTβR and HVEM in the same cell.We used cell lines with different relative expression of HVEM and LTβR to show that LIGHT-induced signals mediated by these receptors were associated with altered TRAF2 stability andRelA nuclear translocation. Production of the inflammatory chemokine CXCL10 was primarily mediated by LTβR. Higher expression of HVEM was associated with cell survival, while unopposed LTβR signaling favored pathways leading to apoptosis. Importantly, restoring HVEM expression in cells with low endogenous expression recapitulated the phenotype of cells with higher endogenous expression. Together, our data provide evidence that relative expression of HVEM and LTβR modulatescanonical NF-κB and pro-apoptotic signals stimulated by LIGHT.
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影响因子：
32.4
作者：
Dejardin, E;Droin, NM;Green, DR
通讯作者：
Green, DR
DOI：
10.1073/pnas.0902115106
发表时间：
2009-04-14
影响因子：
11.1
作者：
Cheung, Timothy C.;Steinberg, Marcos W.;Ware, Carl F.
通讯作者：
Ware, Carl F.
影响因子：
16
作者：
Ea, CK;Deng, L;Chen, ZJJ
通讯作者：
Chen, ZJJ
影响因子：
4.8
作者：
Harrop, JA;McDonnell, PC;Young, PR
通讯作者：
Young, PR
影响因子：
3.6
作者：
Hosokawa, Yoshitaka;Hosokawa, Ikuko;Matsuo, Takashi
通讯作者：
Matsuo, Takashi