Regulation of prostaglandin synthesis by interleukin-1β in cultured bovine luteal cells

Abstract

Prostaglandins produced within the CL may serve as local modulators of CL function. The present study was designed to characterize the cellular mechanisms by which the cytokine interleukin-1β (IL-1β) stimulates prostaglandin production in cultured luteal cells. Cycloheximide (CHX) and actinomycin D (Act D) did not affect basal, but completely inhibited IL-1β- stimulated prostaglandin F(2α) (PGF(2α)) production (p < 0.05). The phospholipase A2 (PLA2) inhibitor, aristolochic acid (PLA2X), and the phospholipase C (PLC) inhibitor, compound 48/80 (PLCX), suppressed IL-1β- stimulated (p < 0.05), but not basal, PGF(2α) production. The addition of exogenous arachidonic acid (AA) restored the stimulatory effect of IL-1β in PLCX-treated, but not in PLA2X-treated, cells, suggesting that PLA2 is a key regulatory point of IL-1β action. Chronic exposure of the luteal cells to IL-1β resulted in stimulatory effects beyond that of increasing AA availability, presumably by up-regulation of prostaglandin endoperoxide (PGH) synthase. Chronic exposure of luteal cells to IL-1β also inhibited progesterone production, but this effect appeared to be independent of endogenous PGF(2α) production. The ability of IL-1β to comprehensively stimulate luteal PGF(2α) production while inhibiting luteal progesterone production is suggestive that IL-1β may facilitate regression of the CL.