Analysis of Tlr4-mediated LPS signal transduction in macrophages by mutational modification of the receptor
Analysis of Tlr4-mediated LPS signal transduction in macrophages by mutational modification of the receptor
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DOI：
10.1006/bcmd.1999.0262
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发表时间：
1999-11-15
影响因子：
2.3
通讯作者：
Beutler, B
中科院分区：
文献类型：
--
作者：
Du, X;Poltorak, A;Beutler, B
In mouse macrophages (RAW 264.7 cells), toll-like receptor 4 (Tlr4) is a limiting factor in lipopolysaccharide (LPS) signal transduction. The expression of only 1-2 x 10(4) copies of recombinant Tlr4 per cell enhances sensitivity to LPS, shifting the EC50 by 30-fold to the left. Expression of the Tlr4(Lps-d) isoform of Tlr4 (found in C3H/HeJ mice) shifts the EC50 2600-fold to the right, essentially abolishing LPS responses. A truncated form of Tlr4, lacking a cytoplasmic domain, exerts only a weak inhibitory effect on signal transduction. Similarly, the normal or Tlr4(Lps-d) forms of protein lacking a cytoplasmic domain, cause modest inhibition of LPS signaling. Manipulations of Tlr4 structure and expression cause changes in LPS sensitivity that range over 3 to 4 orders of magnitude. These findings support the view that Tlr4 is an integral component of a solitary pathway for LPS signal transduction in macrophages and permit inferences related to the mechanism of signaling and its blockade.
