Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction
Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction
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DOI：
10.1074/jbc.274.16.10689
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发表时间：
1999-04-16
影响因子：
4.8
通讯作者：
Gusovsky, F
中科院分区：
文献类型：
--
作者：
Chow, JC;Young, DW;Gusovsky, F
TLR4是最近发现的toll样受体蛋白家族的一员，被认为是Lps，是哺乳动物对脂多糖产生有效反应所必需的基因。为了确定TLR4是否参与脂多糖诱导的核因子- κ B （nf - κ B）途径的激活，我们用人TLR4 cDNA和nf - κ B依赖性荧光素酶报告质粒短暂转染HEK 293细胞，然后用脂多糖/CD14复合物刺激。结果表明，脂多糖以剂量和时间依赖的方式刺激转染TLR4基因的细胞中nf - κ b介导的基因表达。此外，脂多糖拮抗剂E5531以剂量依赖的方式阻断tlr4介导的转基因激活（IC50类似于30 nM）。这些数据表明，TLR4参与脂多糖信号传导，并作为CD14的细胞表面共受体，导致脂多糖介导的nf - κ B激活和随后的细胞事件。
TLR4 is a member of the recently identified Toll-like receptor family of proteins and has been putatively identified as Lps, the gene necessary for potent responses to lipopolysaccharide in mammals. In order to determine whether TLR4 is involved in lipopolysaccharide-induced activation of the nuclear factor-kappa B (NF-kappa B) pathway, HEK 293 cells were transiently transfected with human TLR4 cDNA and an NF-kappa B-dependent luciferase reporter plasmid followed by stimulation with lipopolysaccharide/CD14 complexes. The results demonstrate that lipopolysaccharide stimulates NF-kappa B-mediated gene expression in cells transfected with the TLR4 gene in a dose- and time-dependent fashion. Furthermore, E5531, a lipopolysaccharide antagonist, blocked TLR4-mediated transgene activation in a dose-dependent manner (IC50 similar to 30 nM). These data demonstrate that TLR4 is involved in lipopolysaccharide signaling and serves as a cell-surface co-receptor for CD14, leading to lipopolysaccharide-mediated NF-kappa B activation and subsequent cellular events.