Toll-like receptor 4 mutation impairs the macrophage TNFalpha response to peptidoglycan.
Toll-like receptor 4 mutation impairs the macrophage TNFalpha response to peptidoglycan.
复制标题
Toll 样受体 4 突变会损害巨噬细胞 TNFα 对肽聚糖的反应。
DOI:
10.1016/j.bbrc.2004.10.008
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发表时间:
2004
期刊:
影响因子:
--
通讯作者:
Cherayil,BobbyJ
中科院分区:
文献类型:
--
作者:
Li,Qian;Cherayil,BobbyJ
Macrophages produce TNFα when infected by bacteria, a response that follows recognition of microbial components by members of the Toll-like receptor (TLR) family. Cells that lack functional TLR4 are known to have markedly diminished responses to Gram-negative lipopolysaccharide. We demonstrate in the present work that peritoneal macrophages derived from strains of mice that carry a spontaneous, inactivating mutation in TLR4 also have impaired production of TNFα in response to peptidoglycan, a ligand for TLR2. This impairment is at a step of biosynthesis subsequent to the generation of mRNA. TLR4-activated signals act at this step to enhance peptidoglycan-induced TNFα production in wild-type mice. Based on these observations, we conclude that macrophages from wild-type mice are primed by chronically acting TLR4 signals, probably resulting from exposure to environmental lipopolysaccharide. These signals are required for optimal production of TNFα in response to TLR2 stimulation, and are absent in macrophages from TLR4 mutant animals.