Molecular basis for tumor necrosis factor-induced increase in pulmonary superoxide dismutase activities.

Tracheal insufflation of tumor necrosis factor (TNF) enhances pulmonary antioxidant enzyme activities and protects rats against oxygen toxicity (J. Appl. Physiol. 68: 1211-1219, 1990). We now report that tracheal insufflation of TNF selectively induced pulmonary Mn-superoxide dismutase (SOD) mRNA in normoxia- and hyperoxia-exposed rats, leading to increased amounts of Mn-SOD specific protein and enzyme activity. Tracheal insufflation of TNF had no effect on the levels of pulmonary Cu,Zn-SOD mRNA or specific protein. Hyperoxia alone also selectively induced pulmonary Mn-SOD mRNA. However, the hyperoxia-induced increase in Mn-SOD mRNA was not associated with an increase in Mn-SOD specific protein or enzyme activity. The results suggest that the increased pulmonary Mn-SOD in TNF-insufflated rats may contribute to the TNF-induced protection against oxygen toxicity.