DISSOCIATION BETWEEN INTERLEUKIN-1-BETA-INDUCED EXPRESSION OF MESSENGER-RNA FOR SUPEROXIDE-DISMUTASE AND NITRIC-OXIDE SYNTHASE IN INSULIN-PRODUCING CELLS

We presently investigated the induction of manganese superoxide dismutase (MnSOD) and nitric oxide synthase (iNOS) mRNA by interleukin-1 beta (IL-1 beta) in insulin-producing RINm5F cells. IL-1 beta induced both mRNAs in parallel, with increased levels detectable after 4 h and further increase at 6 h. Aminoguanidine, a blocker of NO production, did not prevent IL-1 beta-induced MnSOD mRNA expression, and SNP, a NO releasing agent, did not induce MnSOD mRNA. Actinomycin D, an inhibitor of gene transcription, prevented IL-1 beta induction of both MnSOD and iNOS mRNA. Cycloheximide, an inhibitor of protein synthesis, prevented IL-1 beta-induced expression of iNOS mRNA, but not MnSOD mRNA. These data suggest that induction of MnSOD mRNA by IL-1 beta is independent of iNOS expression and NO production. Moreover, while expression of iNOS mRNA depends on protein synthesis, MnSOD mRNA induction does not necessarily require this step. Thus, it seems that IL-1 induces genes potentially involved in cell damage (NOS) and defense (MnSOD) by different mechanisms. (C) 1994 Academic Press, Inc.