TRAIL receptor mediates inflammatory cytokine release in an NF-κB-dependent manner  

作　　者：Wanhu Tang Weimin Wang Yaxi Zhang Shilian Liu Yanxin Liu Dexian Zheng 

机构地区：[1]National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China

出　　处：《Cell Research》2009年第6期758-767,共10页细胞研究（英文版）

基　　金：We thank Drs Hongbing Shu （Wuhan University, China）, Jiandong Li （University of Rochester Medical Center, USA）, Andrew Thorbum （University of Colorado Comprehensive Cancer Center, USA） and Andreas Strasser （The Walter and Eliza Hall Institute of Medical Research, Australia） for the generous gifts of the constructs. This work was partially supported by the National Natural Science Foundation of China （Grants 30571687 and 30721063） and the State Key Basic Research Program of China （Grant 2007CB507404）.

摘　　要：In the present article, we report that DR4 or DR5 overexpression dramatically activates the release of the inflammatory cytokines IL-8, TNF-α, CCL20, MIP-2 and MIP-1β in an NF-κB-dependent manner in 293T, MDA-MB-231 and HCT-116 cells. We showed that death receptor-mediated signals were extracellular domain-independent, whereas the effect of overexpression of the DR4 intracellular domain was much less potent. The TRADD-TRAF2-NIK- IKKα/β signaling cascade, which plays an essential role in TNF-induced NF-κB activation, was found to be involved in tumor necrosis factor-related apoptosis-inducing ligand （TRAIL） receptor-mediated signal transduction. The FADD-caspase signaling pathway, which has been reported to be mostly related to apoptosis, was identified as being essential for DR4 or DR5 overexpression-mediated NF-κB activation and cytokine secretion and crosstalks with the TRADD-TRAF2-NIK-IKKα/β signaling cascade. Furthermore, a DR5 agonistic antibody （AD5-10） triggered the inflammatory cytokine release. These data, together with previous reports, provide strong evidence that TRAIL and TRAIL receptors play an important role in inflammation.

关 键 词：TRAIL receptor INFLAMMATION CYTOKINE NF-ΚB 

分 类 号：Q523[生物学—生物化学] S856.9[农业科学—临床兽医学]