Document Detail

Thiopental inhibits NF-kappaB activation in human glioma cells and experimental brain inflammation.
MedLine Citation:
PMID:  11489444     Owner:  NLM     Status:  MEDLINE    
Thiopental is one of the intravenous anesthetics used widely. Several reports have demonstrated that thiopental inhibits the immune responses. We investigated whether or not thiopental inhibits the production of tumor necrosis factor-alpha (TNF-alpha) induced by lipopolysaccharide (LPS) in human glioma cells (A-172). Moreover, we determined whether or not thiopental modulates activation of the transcription factor NF-kappaB, a factor that regulates expression of the genes that code for proinflammatory cytokines in A-172 cells and in experimental murine brain inflammation. Thiopental inhibited TNF-alpha production induced by LPS in A-172 cells. Electrophoretic mobility shift assays demonstrated that thiopental inhibited NF-kappaB activation induced by LPS in A-172 cells. In experimental murine brain inflammation induced by intracerebroventricular injection of LPS, intraperitoneal injection of thiopental inhibited NF-kappaB activation. Western blot analysis indicated that this inhibition was linked to preservation of IkappaBalpha protein expression in A-172 cells. The chloramphenicol acetyltransferase assay revealed that NF-kappaB-dependent reporter gene expression was suppressed in A-172 cells exposed to thiopental. These findings are consistent with the idea that thiopental exerts antiinflammatory effects in cultured cells and experimental murine brain inflammation, through suppression of TNF-alpha production via inhibition of NF-kappaB activation.
T Ichiyama; M Nishikawa; J M Lipton; T Matsubara; H Takashi; S Furukawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Brain research     Volume:  911     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-07     Completed Date:  2001-10-11     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  56-61     Citation Subset:  IM    
Department of Pediatrics, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube 755-8505, Japan.
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MeSH Terms
Anesthetics, Intravenous / pharmacology*
Brain / drug effects*,  immunology,  physiopathology
Brain Neoplasms
DNA-Binding Proteins / metabolism
Encephalitis / chemically induced,  drug therapy*,  metabolism
Gene Expression Regulation / drug effects,  physiology
Genes, Reporter / drug effects,  physiology
I-kappa B Proteins*
Immune System / drug effects,  metabolism
Lipopolysaccharides / pharmacology
Mice, Inbred BALB C
NF-kappa B / drug effects*,  genetics,  metabolism
Thiopental / pharmacology*
Tumor Cells, Cultured / drug effects*,  immunology,  metabolism
Tumor Necrosis Factor-alpha / drug effects*,  metabolism
Reg. No./Substance:
0/Anesthetics, Intravenous; 0/DNA-Binding Proteins; 0/I-kappa B Proteins; 0/Lipopolysaccharides; 0/NF-kappa B; 0/Tumor Necrosis Factor-alpha; 139874-52-5/NF-kappaB inhibitor alpha; 76-75-5/Thiopental

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