Oxygen free radicals mediate the induction of manganese superoxide dismutase gene expression by TNF-alpha.

In this study, the hypothesis that oxygen free radicals act as intracellular messengers is examined. Treatment of human oral carcinoma SCC-25 cells with 200 ng/ml human TNF-alpha for 6 h greatly increased manganese superoxide dismutase (MnSOD) gene expression as detected by western blotting, RT-PCR, and nuclear run-on experiments. In the presence of the oxygen free radical spin trapping reagent, 5,5-dimethyl pyrroline-N-oxide (DMPO), the induction of MnSOD gene expression by TNF-alpha was significantly reduced. Electron paramagnetic resonance experiments showed that the production of oxygen free radicals was enhanced in TNF-alpha treated cells. Taken together, these observations suggest that the induction of MnSOD expression by TNF-alpha is at least partially mediated by intracellular formation of oxygen free radicals, and that superoxide is most likely the initiating species involved in the mediation of MnSOD gene expression by TNF-alpha.