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

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-α 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-α was significantly reduced. Electron paramagnetic resonance experiments showed that the production of oxygen free radicals was enhanced in TNF-α treated cells. Taken together, these observations suggest that the induction of MnSOD expression by TNF-α 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-α.