SHP-1 inhibits LPS-mediated TNF and iNOS production in murine macrophages
SHP-1 inhibits LPS-mediated TNF and iNOS production in murine macrophages
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DOI：
10.1016/j.bbrc.2006.02.005
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发表时间：
2006-04-07
影响因子：
3.1
通讯作者：
English, BK
中科院分区：
文献类型：
--
作者：
Hardin, AO;Meals, EA;English, BK
一些证据表明，蛋白酪氨酸磷酸酶，包括CD 45和SHP-1，调节巨噬细胞活化。来自缺乏SHP-1的小鼠（蛾化小鼠）的巨噬细胞对人刺激具有高反应性，表明SHP-1可以负调节巨噬细胞活化。在此，我们报告说，抑制/诱导的野生型SHP-1的过表达RAW 264.7巨噬细胞（RAW-TT 10细胞）的亚克隆抑制TNF分泌和iNOS蛋白的积累与脂多糖（LPS）和重组鼠干扰素gammia刺激，并导致减少LPS介导的酪氨酸磷酸化的vav 1。与此相反，表达截短的SHP-1构建体先前显示干扰内源性SHP-1功能适度增强LPS介导的TNF和iNOS的生产，并不抑制vav 1酪氨酸磷酸化。总之，这些数据提供了第一个直接的证据表明，SHP-1抑制巨噬细胞激活的LPS，并表明这种效果可能是介导的vav 1的去磷酸化的一部分。(c)2006年爱思唯尔公司All rights reserved.
Several lines of evidence have suggested that protein tyrosine phosphatases, including CD45 and SHP-1, regulate macrophage activation. Macrophages from mice lacking SHP-1 (motheaten mice) are hyper-responsive to man), stimuli, suggesting that SHP-1 may negatively regulate macrophage activation. Herein we report that the repressible/inducible over-expression of wild-type SHP-1 in a subclone of RAW 264.7 macrophages (RAW-TT 10 cells) inhibited both TNF secretion and iNOS protein accumulation in response to stimulation with lipopolysaccharide (LPS) and recombinant murine interferon-gamnia and led to diminished LPS-mediated tyrosine phosphorylation of vav1. In contrast, expression of a truncated SHP-1 construct previously shown to interfere with endogenous SHP-1 function modestly augmented LPS-mediated TNF and iNOS production and did not inhibit vav1 tyrosine phosphorylation. Taken together, these data provide the first direct evidence that SHP-1 inhibits macrophage activation by LPS and suggest that this effect may be mediated in part by dephosphorylation of vav1. (c) 2006 Elsevier Inc. All rights reserved.