REGULATION OF HEME OXYGENASE MESSENGER-RNA IN MESANGIAL CELLS - PROSTAGLANDIN E(2), NEGATIVELY MODULATES INTERLEUKIN-1-INDUCED HEME OXYGENASE-1 MESSENGER-RNA

Heme oxygenase (EC 1.14.99.3) is the rate-limiting enzyme in heme catabolism. Several lines of evidence suggest a possible role for heme oxygenase in the inflammatory process and in cellular signaling. We have evaluated the regulation of heme oxygenase-1 mRNA induction by the inflammatory stimuli, phorbol 12,13-myristate acetate, heat shock and interleukin-1 beta in cultured rat mesangial cells. Phorbol 12,13-myristate acetate and heat shock rapidly (maximal at 2-3 hrs) induced heme oxygenase-1 mRNA. The effect of interleukin-1 beta on heme oxygenase-1 mRNA induction was slower (maximal at 12 hrs) and modest. However, in the presence of a cyclooxygenase inhibitor, indomethacin, interleukin-1 beta strongly induced heme oxygenase-1 mRNA. The addition of exogenous PGE(2) reversed the effect of indomethacin. These data suggest that pro-inflammatory stimuli increase heme oxygenase-1 mRNA expression in rat mesangial cells and that interleukin-1 beta-induced heme oxygenase-1 mRNA level is negatively modulated by PGE(2). (C) 1995 Academic Press, Inc.