MITOCHONDRIAL SUPEROXIDE-DISMUTASE INDUCTION DOES NOT PROTECT EPITHELIAL-CELLS DURING OXIDANT EXPOSURE IN-VITRO

The significance of manganese superoxide dismutase (MnSOD) induction i n cells and tissues during oxidant stress is still poorly understood. In this study, transformed human bronchial epithelial cells (BEAS 2B) were treated with interferon-gamma (IFN-gamma), tumor necrosis factor- alpha (TNF-alpha), or with combination of these cytokines (10 ng/ml co ncentrations) for 48 or 72 h and exposed to selected oxidants. TNF-alp ha and IFN-gamma+TNF-alpha combination resulted in a marked increase o f MnSOD protein and MnSOD activity. When cells pretreated with the cyt okines were exposed to hyperoxia (95% O-2, 72 h), menadione (5-50 mu M , 4 h), or H2O2 (0.5 and 5 mM, 4 h), in all cases IFN-gamma and TNF-al pha enhanced oxidant-related cell injury. The effect was most signific ant with cells pretreated with a combination of IFN-gamma and TNF-alph a. Antioxidant enzymes such as total SOD, glutathione peroxidase, glut athione reductase, and glucose-6-phosphate dehydrogenase did not chang e significantly during the cytokine treatment. Catalase activity was n ot changed by IFN-gamma or TNF-alpha but it decreased significantly (3 4%) in IFN-gamma+TNF-alpha-treated cells. Free radical generation was not changed by these cytokines in acute (30 min) experimental conditio ns or after 48-h treatment. These results suggest that cytokine-induce d MnSOD does not protect bronchial epithelial cells against endogenous ly or exogenously generated oxidants in vitro. In fact, cells that con tained the highest MnSOD activity were the most sensitive to subsequen t oxidant damage.