REGULATION OF PROSTAGLANDIN SYNTHESIS BY INTERLEUKIN-1-BETA IN CULTURED BOVINE LUTEAL CELLS

Prostaglandins produced within the CL may serve as local modulators of CL function. The present study was designed to characterize the cellu lar mechanisms by which the cytokine interleukin-1 beta (IL-1 beta) st imulates prostaglandin production in cultured luteal cells. Cyclohexim ide (CHX) and actinomycin D (Act D)did not affect basal, but completel y inhibited IL-1 beta-stimulated prostaglandin F-2 alpha (PGF(2 alpha) ) production (p < 0.05). The phospholipase A(2) (PLA(2)) inhibitor, ar istolochic acid (PLA(2)X), and the phospholipase C (PLC) inhibitor, co mpound 48/80 (PLCX), suppressed IL-1 beta-stimulated (P < 0.05), but n ot basal, PGF(2 alpha) production. The addition of exogenous arachidon ic acid (AA) restored the stimulatory effect of IL-1 beta in PLCX-trea ted, but not in PLA(2)X-treated, cells, suggesting that PLA(2) is a ke y regulatory point of IL-1 beta action. Chronic exposure of the luteal cells to IL-1 beta resulted in stimulatory effects beyond that of inc reasing AA availability, presumably by up-regulation of prostaglandin endoperoxide (PGH) synthase. Chronic exposure of luteal cells to IL-1 beta also inhibited progesterone production, but this effect appeared to be independent of endogenous PGF(2 alpha) production. The ability o f IL-1 beta to comprehensively stimulate luteal PGF(2 alpha) productio n while inhibiting luteal progesterone production is suggestive that I L-1 beta may facilitate regression of the CL.