title: Differential induction of TNF-alpha and MnSOD by endotoxin: role of reactive oxygen species and NADPH oxidase.
abstract: Endotoxin (lipopolysaccharide [LPS]) is known to induce the production of tumor necrosis factor (TNF)-alpha and the induction of manganese superoxide dismutase (MnSOD). We have recently demonstrated that induction of TNF-alpha and MnSOD by LPS is mediated through different signal transduction pathways. In the current study, we investigated the role of reactive oxygen species (ROS) in the induction of TNF-alpha and MnSOD messenger RNAs (mRNAs) in human monocytes. Hypoxia (1% O2) inhibited the production of superoxide (O2-) and the induction of MnSOD, but not TNF-alpha, mRNA. Diphenylene iodonium (DPI), a potent inhibitor of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, had no effect on LPS induction of MnSOD mRNA, whereas it markedly inhibited LPS-induced O2- production. Neither hypoxia nor DPI had any effect on LPS activation of nuclear factor (NF)-kappaB. These results suggest that (1) ROS is important in the induction of MnSOD, but not TNF-alpha, mRNA by LPS, (2) ROS from sources other than NADPH oxidase is involved in LPS induction of MnSOD mRNA, and (3) ROS-mediated LPS induction of MnSOD mRNA is independent of NF-kappaB activation.
authors.affiliation: Research Service, Stratton Veterans Affairs Medical Center, Albany Medical College, 113 Holland Ave., Albany, NY 12208, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: White
authors.forename: M F
authors.initials: MF
authors.lastname: Tsan
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D015152:Blotting, Northern; D015687:Cell Hypoxia / Q000235:genetics; D002460:Cell Line; D004587:Electrophoresis, Agar Gel; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006801:Humans; D009000:Monocytes / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000502:physiology*; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001713:Biphenyl Compounds; D004731:Endotoxins; D016328:NF-kappa B; D009861:Onium Compounds; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C031291:diphenyliodonium; D013481:Superoxides; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate