Am. J. Respir. Cell Mol. Biol., Volume 24, Number 2, February, 2001 164-169

Differential Induction of TNF- and MnSOD by Endotoxin
Role of Reactive Oxygen Species and NADPH Oxidase

Julie E. White and Min-Fu Tsan

Research Service, Stratton Veterans Affairs Medical Center, and Department of Medicine and Center for Cardiovascular Sciences, Albany Medical College, Albany, New York

Endotoxin (lipopolysaccharide [LPS]) is known to induce the production of tumor necrosis factor (TNF)- and the induction of manganese superoxide dismutase (MnSOD). We have recently demonstrated that induction of TNF- 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- 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-, 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)-B. These results suggest that (1) ROS is important in the induction of MnSOD, but not TNF-, 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-B activation.

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