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Ketamine Inhibits Lipopolysaccharide-Induced Astrocytes Activation by Suppressing TLR4/NF-ĸB Pathway.
MedLine Citation:
PMID:  22832327     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background/Aims: Ketamine has been reported to exert anti-inflammatory effects on astrocytes stimulated by lipopolysaccharide (LPS) in vitro and in vivo. However, the mechanism has not been elicited clearly. The aim of this study was to investigate the effects of ketamine on TLR4 expression and NF-ĸB-p65 phosphorylation, as well as the production of proinflammatory cytokines in LPS challenged astrocytes. Methods: Astrocytes were stimulated with LPS (1µg/ ml) in the absence and presence of various concentrations of ketamine (10, 100, 1000µM). The concentrations of IL-1β, IL-6 and TNF-α were measured by ELISA, the expression of glial fibrillary acidic protein (GFAP) in astrocytes was detected by immunofluorescence staining, the level of phosphorylated NF-ĸB p65 and the expression of TLR4 were detected by western blotting. Results: LPS increased TLR4 expression and the phosphorylation of NF-ĸB p65 subunit as well as GFAP expression and the production of IL-1β, IL-6 and TNF-α in cultured astrocytes. Ketamine (100 and 1000 µM) reduced the expression of GFAP and the production of these proinflammatory cytokines, inhibited the expression of TLR4 and attenuated the phosphorylation of NF-ĸB p65 in astrocytes challenged by LPS. Conclusion: The inhibitory effects of ketamine on LPS-induced astrocytes activation and inflammation response may be mediated by suppressing NF-ĸB activation through reducing the expression of TLR4.
Authors:
Yuqing Wu; Wei Li; Ce Zhou; Fuzhao Lu; Tianhui Gao; Yingchun Liu; Junli Cao; Yongmei Zhang; Yong Zhang; Chenghua Zhou
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-27
Journal Detail:
Title:  Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology     Volume:  30     ISSN:  1421-9778     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9113221     Medline TA:  Cell Physiol Biochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  609-617     Citation Subset:  -    
Copyright Information:
Copyright © 2012 S. Karger AG, Basel.
Affiliation:
Department of Anesthetic Pharmacology, Xuzhou Medical College, Xuzhou, PR China.
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