title: The inhibition of lipopolysaccharide-induced tumor necrosis factor-alpha and nitric oxide production by Clostridium perfringens alpha-toxin and its relation to alpha-toxin-induced intracellular ceramide generation.
abstract: The effect of Clostridium perfringens alpha-toxin on production of tumor necrosis factor (TNF)-alpha and nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells was studied. The pretreatment of wild type alpha-toxin, but not the inactive mutant, significantly decreased LPS-induced TNF-alpha and NO production. alpha-Toxin inhibited the expression of TNF-alpha and an inducible type of NO synthase protein and mRNA. Furthermore, it inhibited the phosphorylation of IkappaB-alpha and p65 NF-kappaB subunit, and the NF-kappaB luciferase reporter gene activity in LPS-stimulated cells. The pretreatment of alpha-toxin increased the level of intracellular ceramide. Taken together, Clostridium perfringens alpha-toxin pretreatment was suggested to inhibit LPS-induced TNF-alpha and NO production through the inhibition of NF-kappaB activation. The relationship between alpha-toxin-induced intracellular ceramide generation and the NF-kappaB inhibition is discussed.
authors.affiliation: Department of Microbiology and Immunology, Aichi Medical University, School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors.forename: Gantsetseg
authors.initials: G
authors.lastname: Tumurkhuu
authors.forename: Naoki
authors.initials: N
authors.lastname: Koide
authors.forename: Jargalsaikhan
authors.initials: J
authors.lastname: Dagvadorj
authors.forename: Abu Shadat Mohammod
authors.initials: AS
authors.lastname: Noman
authors.forename: Imtiaz
authors.initials: I
authors.lastname: Iftakhar-E-Khuda
authors.forename: Imtiaz
authors.initials: I
authors.lastname: Iftekar-E-Khuda
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Naiki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Komatsu
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshida
authors.forename: Masataka
authors.initials: M
authors.lastname: Oda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nagahama
authors.forename: Jun
authors.initials: J
authors.lastname: Sakurai
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokochi
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology* / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D002518:Ceramides / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D051550:I-kappa B Kinase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D010738:Type C Phospholipases / Q000276:immunology* / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D002135:Calcium-Binding Proteins; D002518:Ceramides; D008070:Lipopolysaccharides; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D008156:Luciferases; D051550:I-kappa B Kinase; D010738:Type C Phospholipases; C040649:alpha toxin, Clostridium perfringens