INDUCTION OF MANGANESE SUPEROXIDE-DISMUTASE BY CYTOKINES AND LIPOPOLYSACCHARIDE IN CULTURED MOUSE ASTROCYTES

To determine whether cytokines or lipopolysaccharide (LPS) are involve d in the induction of superoxide dismutase (SOD) in the nervous system , we examined the effects of these substances on the levels of SOD in cultured mouse astrocytes. Treatment of astrocytes with 10(2) to 10(4) U/ml tumor necrosis factor-alpha for 3 days increased the levels of M n SOD in a dose- and time-dependent manner to as much as six times the level under nontreated conditions. Treatment with 1.0 mu g/ml LPS for 3 days elicited a fourfold increase in levels of Mn SOD, and the effe ct of LPS was also dose dependent. Furthermore, Mn SOD in astrocytes w as induced by a 3-day exposure to interleukin-1 alpha at concentration s of 10(2) or 10(3) U/ml. However, these stimuli had no effect on leve ls of copper-zinc SOD (Cu/Zn SOD) in astrocytes. By contrast, interfer on-gamma did not change the levels of either Mn or Cu/Zn SOD in the ce lls. The results indicate that the selective induction of Mn SOD by cy tokines and LPS, which has been observed in nonnervous tissues, may al so occur in nervous tissues. The induction of Mn SOD may represent a m echanism for protection of cells from oxidative stress.