Unresponsiveness of MyD88-deficient mice to endotoxin
Unresponsiveness of MyD88-deficient mice to endotoxin
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DOI：
10.1016/s1074-7613(00)80086-2
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发表时间：
1999-07-01
期刊：
影响因子：
32.4
通讯作者：
Akira, S
中科院分区：
文献类型：
--
作者：
Kawai, T;Adachi, O;Akira, S
MyD88是一种通用接头蛋白，在Toll/IL-1受体家族信号转导中发挥重要作用。近年来，Toll样受体2和4(TLR2和TLR4)被认为是脂多糖(LPS)的信号受体。在这项研究中，我们证明了MyD88基因敲除小鼠缺乏通过休克反应、B细胞增殖反应以及巨噬细胞和胚胎成纤维细胞分泌细胞因子来衡量对内毒素的反应能力。然而，在MyD88基因敲除小鼠中，核因子-kappa B和丝裂原激活蛋白(MAP)激酶家族的激活都没有被取消。这些发现表明，通过MyD88的信号转导对于内毒素反应是必不可少的，但MyD88基因敲除小鼠不能诱导依赖于内毒素的基因表达，这不能简单地归因于缺乏MAP激酶和核因子-kappa B的激活。
MyD88 is a general adaptor protein that plays an important role in the Toll/IL-1 receptor family signalings. Recently, Toll-like receptors 2 and 4 (TLR2 and TLR4) have been suggested to be the signaling receptors for lipopolysaccharide (LPS). In this study, we demonstrate that MyD88 knockout mice lack the ability to respond to LPS as measured by shock response, B cell proliferative response, and secretion of cytokines by macrophages and embryonic fibroblasts. However, activation of neither NF-kappa B nor the mitogen-activated protein (MAP) kinase family is abolished in MyD88 knockout mice. These findings demonstrate that signaling via MyD88 is essential for LPS response, but the inability of MyD88 knockout mice to induce LPS-dependent gene expression cannot simply be attributed to lack of the activation of MAP kinases and NF-kappa B.