JAK2-STAT3 signaling pathway mediates thrombin-induced proinflammatory actions of microglia in vitro

被引:79
作者
Huang, Chengfang [1 ]
Ma, Rong [2 ]
Sun, Shenggang [1 ]
Wei, Guirong [1 ]
Fang, Yuan [1 ]
Liu, Rengang [3 ]
Li, Gang [1 ]
机构
[1] Huazhong Univ Sci & Technol, Dept Neurol, Union Hosp, Tongji Med Coll, Wuhan 430022, Peoples R China
[2] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pharmacol, Wuhan 430030, Peoples R China
[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Anat, Wuhan 430030, Peoples R China
关键词
Thrombin; Microglia; JAK2-STAT3; pathway; Dopaminergic neuron; iNOS; TNF-alpha;
D O I
10.1016/j.jneuroim.2008.07.004
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:118 / 125
页数:8
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