Thiopental inhibits NF-kappaB activation in human glioma cells and experimental brain inflammation.
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.
Ichiyama
T
T
Department of Pediatrics, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube 755-8505, Japan. ichiyama@po.cc.yamaguchi-u.ac.jp
Nishikawa
M
M
Lipton
J M
JM
Matsubara
T
T
Takashi
H
H
Furukawa
S
S
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D001932:Brain Neoplasms; D004268:DNA-Binding Proteins / Q000378:metabolism; D004660:Encephalitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D017930:Genes, Reporter / Q000187:drug effects / Q000502:physiology; D005910:Glioma; D006801:Humans; D020672:I-kappa B Proteins; D007107:Immune System / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013874:Thiopental / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism
D018686:Anesthetics, Intravenous; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D013874:Thiopental