| Literature DB >> 18710787 |
Chengfang Huang1, Rong Ma, Shenggang Sun, Guirong Wei, Yuan Fang, Rengang Liu, Gang Li.
Abstract
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.Entities:
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Year: 2008 PMID： 18710787 DOI： 10.1016/j.jneuroim.2008.07.004
Source DB: PubMed Journal: J Neuroimmunol ISSN： 0165-5728 Impact factor: 3.478