Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway

被引：571

作者：

He, Sudan ^{[1
]}

Liang, Yuqiong ^{[2
]}

Shao, Feng ^{[2
]}

Wang, Xiaodong ^{[2
]}

机构：

[1] Soochow Univ, Affiliated Hosp 1, Jiangsu Inst Hematol, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China

[2] Nat Inst Biol Sci, Beijing 102206, Peoples R China

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 50期

基金：

中国国家自然科学基金;

关键词：

necroptosis; bone marrow-derived macrophage; NF-KAPPA-B; INDUCED CELL-DEATH; TNF-ALPHA; PROTEIN; INHIBITION; APOPTOSIS; MICE; DOMAIN; LIPOPOLYSACCHARIDE; RECOGNITION;

D O I：

10.1073/pnas.1116302108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We report here that mouse macrophages undergo receptor-interacting kinase-3 (RIP3)-dependent but TNF-alpha-independent necrosis when Toll-like receptors (TLR) 3 and 4 are activated by poly(I: C) and LPS, respectively. An adaptor protein, Toll/IL-1 receptor domain-containing adapter inducing IFN-beta (TRIF/TICAM-1), which is dispensable for TNF-alpha-induced necrosis, forms a complex with RIP3 upon TLR3/TLR4 activation and is essential for TLR3/TLR4-induced necrosis. Mice without RIP3 or functional TRIF did not show macrophage loss and elevation of inflammatory cytokines when they were exposed to LPS. Necrosis in mouse macrophages induced by either TNFR or TLR3/TLR4 is executed by reactive oxygen species. Taken together, these data indicate that there are multiple upstream necrosis-initiating signaling pathways converging on the RIP3 during an innate immune response to viral and bacterial infections in mammals.

引用

页码：20054 / 20059

页数：6

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