Interleukin-1 β independently stimulates production of prostaglandin E 2 and cyclic AMP from human decidual cells

Abstract

Interleukin-1 β (IL-1 β) increased the production of cyclic AMP and prostaglandin E 2 (PGE 2) by cultured human decidual cells during 24 h of stimulation, but not over short incubation times (< 6 h). At concentrations of IL-1 β ranging from 1 to 100 pg/ml, there were parallel changes in cyclic AMP and PGE 2 levels, but 1000 pg of IL-1 β/ml inhibited cyclic AMP production while still stimulating PGE 2 synthesis. The possible link between cyclic AMP and PGE 2 was therefore studied further. Inhibition of IL-1β-stimulated PGE 2 synthesis by indomethacin and direct addition of PGE 2 had no effect on cyclic AMP levels, indicating that PGE 2 did not increase cyclic AMP production by human decidual cells and confirming the independent synthesis of cyclic AMP and PGE 2. The increase in cyclic AMP production induced by IL-1 β is dependent on protein synthesis, but it is not known which component of the adenylate cyclase is increased. A phosphodiesterase inhibitor potentiated the effects of IL-1β on cyclic AMP synthesis, indicating that the cytokine may increase cyclic AMP metabolism. We suggest that high concentrations of IL-1β activate phosphodiesterase activity more than adenylate cyclase, which gives rise to the low levels of cyclic AMP noted above. IL-1 β also decreased forskolin-stimulated cyclic AMP production, which again indicates increased cyclic AMP metabolism. Since most concentrations of IL-1β alone increased cyclic AMP levels, this stimulation must out-weigh the increase in metabolism apparent in the presence of forskolin, phosphodiesterase inhibitor or high levels of interleukin. It is clear that IL-1β increased decidual PGE 2 production independently of cyclic AMP, and that other second messenger must mediate the action of this cytokine.