Regulation of Heme Oxygenase Messenger-RNA in Mesangial Cells - Prostaglandin E₂, 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-1β 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-1β on heme oxygenase-1 mRNA induction was slower (maximal at 12 hrs) and modest. However, in the presence of a cyclooxygenase inhibitor, indomethacin, interleukin-1β strongly induced heme oxygenase-1 mRNA. The addition of exogenous PGE₂ 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-1β-induced heme oxygenase-1 mRNA level is negatively modulated by PGE₂.