Document Detail

Thrombin induces suppressor of cytokine signaling 3 expression in brain microglia via protein kinase Cdelta activation.
MedLine Citation:
PMID:  15081412     Owner:  NLM     Status:  MEDLINE    
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.
Myung-Soon Yang; Jeehyung Lee; Kyung-Ae Ji; Kyoung-jin Min; Myung Ae Lee; Ilo Jou; Eunhye Joe
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  317     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-04-14     Completed Date:  2004-05-19     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  811-6     Citation Subset:  IM    
Neuroscience graduate program, Ajou University School of Medicine, Suwon 442-721, Republic of Korea.
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MeSH Terms
Base Sequence
Blotting, Northern
Brain / enzymology*
DNA Primers
Enzyme Activation
Microglia / enzymology,  metabolism*
Protein Kinase C / metabolism*
Protein Kinase C-delta
RNA, Messenger / genetics
Repressor Proteins / genetics*
Suppressor of Cytokine Signaling Proteins
Thrombin / physiology*
Transcription Factors / genetics*
Reg. No./Substance:
0/DNA Primers; 0/RNA, Messenger; 0/Repressor Proteins; 0/SOCS3 protein, human; 0/Suppressor of Cytokine Signaling Proteins; 0/Transcription Factors; EC Kinase C; EC Kinase C-delta; EC

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