Interleukin-1 beta independently stimulates production of prostaglandin E2 and cyclic AMP from human decidual cells.
Interleukin-1 beta (IL-1 beta) increased the production of cyclic AMP and prostaglandin E2 (PGE2) by cultured human decidual cells during 24 h of stimulation, but not over short incubation times (< 6 h). At concentrations of IL-1 beta ranging from 1 to 100 pg/ml, there were parallel changes in cyclic AMP and PGE2 levels, but 1000 pg of IL-1 beta/ml inhibited cyclic AMP production while still stimulating PGE2 synthesis. The possible link between cyclic AMP and PGE2 was therefore studied further. Inhibition of IL-1 beta-stimulated PGE2 synthesis by indomethacin and direct addition of PGE2 had no effect on cyclic AMP levels, indicating that PGE2 did not increase cyclic AMP production by human decidual cells and confirming the independent synthesis of cyclic AMP and PGE2. The increase in cyclic AMP production induced by IL-1 beta 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-1 beta on cyclic AMP synthesis, indicating that the cytokine may increase cyclic AMP metabolism. We suggest that high concentrations of IL-1 beta activate phosphodiesterase activity more than adenylate cyclase, which gives rise to the low levels of cyclic AMP noted above. IL-1 beta also decreased forskolin-stimulated cyclic AMP production, which again indicates increased cyclic AMP metabolism. Since most concentrations of IL-1 beta 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-1 beta increased decidual PGE2 production independently of cyclic AMP, and that other second messenger must mediate the action of this cytokine.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis* / Q000494:pharmacology; D003656:Decidua / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*
D007375:Interleukin-1; D005576:Colforsin; D000242:Cyclic AMP; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine