Journal Article

Prostaglandin (PG) FP and EP1 receptors mediate PDF2α and PGE2 regulation of interleukin-1β expression in Leydig cell progenitors

Prostaglandins (PG) mediate IL-1ß regulation of several interleukin mRNAs in progenitor Leydig cells. PGE and PGF potently reverse indomethacin (INDO; a cyclooxygenase inhibitor) inhibition of IL-1ß autoinduction. IL-1ß increases PGE and PGF production. To determine the PG receptors involved in this regulation, this study established by RT-PCR and Western analyses which specific receptors for PGE (EP receptors) and PGF (FP receptors) are expressed in progenitors. Pharmacological characterization of receptors involved in PGE and PGF regulation of IL-1ß mRNA levels was ascertained using real-time PCR analyses. FP, EP, EP, and EP receptor mRNAs and proteins, and an EP receptor subtype were detected. IL-1ß treatment (24-h) significantly decreased EP receptor levels; INDO abrogated this down-regulation. FP, EP, and EP receptor levels increased after IL-1ß and IL-1ß + INDO. A selective FP agonist, cloprostenol (0.1 µM), and PGF (10 µM) had similar effects on IL-1ß mRNA levels in progenitors treated with IL-1ß + INDO. None of the EP/EP agonists [butaprost, misoprostol, or 11-deoxy PGE (10 µM)] affected IL-1ß mRNA levels. In contrast, EP/EP agonists (17-phenyltrinor PGE and sulprostone) increased IL-1ß mRNAs in a dose-dependent manner. EP receptor subtype-selective antagonist, SC-51322, blocked IL-1ß-induced and [IL-1ß+ INDO + 17-phenyl trinor PGE]-induced increases in IL-1ßmRNAs. Taken together, our data demonstrate that FP and EP receptors mediate PGF and PGE induction of progenitor IL-1ßexpression.