PYRROLIDINE DITHIOCARBAMATE PREVENTS IL-1-INDUCED NITRIC-OXIDE SYNTHASE MESSENGER-RNA, BUT NOT SUPEROXIDE-DISMUTASE MESSENGER-RNA, IN INSULIN-PRODUCING CELLS

We presently investigated the effects of pyrrolidine dithiocarbamate ( PDTC), a potent inhibitor of nuclear factor kappa B (NF-kappa B), on t he induction of nitric oxide synthase (iNOS) and manganese superoxide dismutase (MnSOD) mRNAs by IL-1 beta in insulin-producing RIN cells. P DTC decreased by 90% both IL-1 beta-induced increase in medium nitrite accumulation (an indicator of NO production) and induction of iNOS mR NA expression. However, PDTC did not prevent induction of MnSOD mRNA b y IL-1 beta. PDTC induced an early (45 min) expression of c-fos mRNA a nd potentiated IL-1 beta-induced c-fos expression. Our data suggest th at NF-kappa B activation is necessary for iNOS, but not for MnSOD, mRN A expression in insulin producing cells. (C) 1995 Academic Press. Inc.