Regulation of prostaglandin endoperoxide synthase gene expression in rat mesangial cells by interleukin-1β

In primary cultures of rat mesangial cells from passage 3 to 6, interleukin-1β (IL-1) induced a time-dependent increase in prostaglandin E₂ (PGE₂) formation and release into the extracellular medium. This increase was associated with a dramatic upregulation of the steady-state levels of mRNA for the prostaglandin endoperoxide synthase (PES)-2 gene transcript as demonstrated by Northern analysis. In contrast, there did not appear to be a significant increase in the mRNA levels for a 2.8-kb transcript for the PES- 1 gene. At 18 h of exposure to IL-1, the steady-state level of message for PES-2 remained elevated at 50% of the 2-h time point. Culturing the cells in the presence of cycloheximide and IL-1 demonstrated a superinduction of the PES-2 message without any change in PES-1 message. The tumor-promoting phorbol ester, phorbol myristate acetate (PMA), was also associated with an upregulation of the message for the PES-2 gene and did not influence the levels of the message for the PES-1 gene as demonstrated by Northern analysis. Dexamethasone (Dex) inhibited to control levels the induction by PMA, but the induction of the message by IL-1 was only inhibited 30%. Despite 70% of the message being present by 2 h of induction, Dex was capable of totally inhibiting the inductive effect of IL-1 with respect to PGE₂ biosynthesis. Immunocytochemical studies demonstrated a dramatic induction of PES-2 protein by IL-1, which was inhibited by Dex. The data suggest that Dex inhibits the translation of the PES-2 protein.