title: Ketamine inhibits lipopolysaccharide-induced astrocytes activation by suppressing TLR4/NF-ĸB pathway.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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: Department of Anesthetic Pharmacology, Xuzhou Medical College, Xuzhou, PR China.
authors: Yuqing
authors: Y
authors: Wu
authors: Wei
authors: W
authors: Li
authors: Ce
authors: C
authors: Zhou
authors: Fuzhao
authors: F
authors: Lu
authors: Tianhui
authors: T
authors: Gao
authors: Yingchun
authors: Y
authors: Liu
authors: Junli
authors: J
authors: Cao
authors: Yongmei
authors: Y
authors: Zhang
authors: Yong
authors: Y
authors: Zhang
authors: Chenghua
authors: C
authors: Zhou
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D007649:Ketamine