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 intracellula r messengers is examined. Treatment of human oral carcinoma SCC-25 cells wi th 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 inductio n of MnSOD gene expression by TNF-alpha was significantly reduced. Electron paramagnetic resonance experiments showed that the production of oxygen fr ee 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 radi cals, and that superoxide is most likely the initiating species involved in the mediation of MnSOD gene expression by TNF-alpha. (C) 2000 Elsevier Sci ence Inc.