JAK2-STAT3 signaling pathway mediates thrombin-induced proinflammatory actions of microglia in vitro
JAK2-STAT3 signaling pathway mediates thrombin-induced proinflammatory actions of microglia in vitro
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JAK2-STAT3信号通路介导凝血酶诱导的小胶质细胞体外促炎作用
DOI：
10.1016/j.jneuroim.2008.07.004
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发表时间：
2008-11-15
影响因子：
3.3
通讯作者：
Li, Gang
中科院分区：
文献类型：
--
作者：
Huang, Chengfang;Ma, Rong;Li, Gang
目前的研究表明，JAK 2-STAT 3炎症信号介导凝血酶刺激的小胶质细胞活化。在大鼠原代小胶质细胞中，凝血酶迅速激活JAK 2并诱导STAT 3磷酸化。此外，凝血酶增加炎症相关基因肿瘤坏死因子（TNF）-α、诱导型一氧化氮合酶（iNOS）的转录，增加TNF-α、NO的产生，并诱导中脑培养物中多巴胺能神经元的神经变性。JAK抑制剂AG 490显著降低凝血酶处理的小胶质细胞中JAK 2和STAT 3的活化。AG 490还抑制凝血酶诱导的TNF-α、iNOS和/或NO释放的转录和表达，并且拯救多巴胺能神经元。这些结果表明，JAK 2-STAT 3信号通路在介导凝血酶诱导的小胶质细胞活化和多巴胺能神经元变性中起关键作用。(C)2008 Elsevier B. V.保留所有权利。
The present study shows that JAK2-STAT3 inflammatory signaling mediates thrombin-stimulated microglia activation. In rat primary microglia, thrombin rapidly activated JAK2 and induced phosphorylation of STAT3. in addition, thrombin increased transcription of the inflammation-associated genes tumor necrosis factor (TNF)-alpha, inducible nitric oxide synthase (iNOS), production of TNF-alpha, NO and induced neurodegeneration of dopaminergic neurons in mesencephalic cultures. AG490, a JAK inhibitor, markedly reduced activation of JAK2 and STAT3 in thrombin-treated microglia. AG490 also inhibited thrombin-induced transcription and expression of TNF-alpha, iNOS and/or NO release, moreover rescued dopaminergic neurons. These results suggest that JAK2-STAT3 signaling pathway plays a critical role in mediating thrombin-induced activation of microglia and degeneration of dopaminergic neurons. (C) 2008 Elsevier B.V. All rights reserved.