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Thrombin induces suppressor of cytokine signaling 3 expression in brain microglia via protein kinase Cdelta activation.

Authors
Yang, MS; Lee, J; Ji, KA; Min, KJ; Lee, MA; Jou, I; Joe, E
Citation
Biochemical and biophysical research communications, 317(3):811-816, 2004
Journal Title
Biochemical and biophysical research communications
ISSN
0006-291X1090-2104
Abstract
Microglia (brain macrophages) are activated upon brain damage. In this study, we demonstrated that thrombin, a pro-inflammatory stimulator of microglia, induced expression of suppressors of cytokine signaling (SOCS) in microglia. RT-PCR analysis and Northern blot analysis showed that thrombin induced SOCS3 mRNA expression. Further experiments indicated SOCS3 expression was not affected by cycloheximide, indicating thrombin directly stimulated SOCS3 transcript expression without de novo protein synthesis. We investigated whether PKCdelta played a role in thrombin-stimulated SOCS3 expression. We found that thrombin activated PKCdelta, and the specific inhibitor of PKCdelta, rottlerin, significantly suppressed thrombin-stimulated SOCS3 expression. In thrombin-pretreated cells, microglial activation-induced by another inflammatory stimulator, lipopolysaccharide, was attenuated compared to that in non-pretreated cells. These results suggest thrombin induce not only proinflammatory mediators but also negative feedback regulators of inflammation, SOCS, which prevent prolonged inflammatory reactions in microglia.
MeSH terms
Base SequenceBlotting, NorthernBrain/*enzymologyDNA PrimersEnzyme ActivationMicroglia/enzymology/*metabolismProtein Kinase C/*metabolismProtein Kinase C-deltaRNA, Messenger/geneticsRepressor Proteins/*geneticsSuppressor of Cytokine Signaling ProteinsThrombin/*physiologyTranscription Factors/*genetics
DOI
10.1016/j.bbrc.2004.03.118
PMID
15081412
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Journal Papers > School of Medicine / Graduate School of Medicine > Brain Science
AJOU Authors
양, 명순이, 명애주, 일로조, 은혜
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