INDUCTION OF PULMONARY MN SUPEROXIDE-DISMUTASE MESSENGER-RNA BY INTERLEUKIN-1

We have previously demonstrated that intratracheal (IT) but not intraperitoneal (IP) administration of 5 mu g tumor necrosis factor (TNF) or interleukin-1 (IL-1) selectively enhances pulmonary Mn superoxide dismutase (Mn SOD) mRNA, leading to increased Mn SOD protein and enzyme activity, and protects rats against O-2 toxicity. In this study, we demonstrated that enhancement of pulmonary Mn SOD mRNA by TNF or IL-1 was highly dependent on the route of administration. IT insufflation of 5 mu g TNF or IL-1 selectively enhanced levels of pulmonary but not splenic or renal Mn SOD mRNA. In contrast, IP or intravenous (IV) administration of TNF (5 mu g) or IL-1 (5, 20, or 50 mu g) had little or no effect on levels of Mn SOD mRNA in the lung, spleen, or kidney. Both TNF and IL-1, whether given by IT, LP, or TV administration, had no effect on levels of Cu,Zn SOD mRNA. IP administration of 2 mg/kg actinomycin D 2 h before IT insufflation of IL-1 paradoxically increased the level of pulmonary Mn SOD mRNA without affecting the level of Cu,Zn SOD or beta-actin mRNA in IL-l-treated rats. Nuclear runoff transcription assay revealed that IT insufflation of IL-1 enhanced the rate of Mn SOD but not Cu,Zn SOD mRNA synthesis. mie conclude that IL-1-induced increase in pulmonary Mn SOD mRNA is at least in part regulated at the transcriptional level.