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

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Article (peer-reviewed)

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Prostaglandins (PG) mediate IL-1β regulation of several interleukin mRNAs in progenitor Leydig cells. PGE2 and PGF potently reverse indomethacin (INDO; a cyclooxygenase inhibitor) inhibition of IL-1β autoinduction. IL-1β increases PGE2 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 PGE2 (EP receptors) and PGF (FP receptors) are expressed in progenitors. Pharmacological characterization of receptors involved in PGE2 and PGF regulation of IL-1β mRNA levels was ascertained using real-time PCR analyses. FP, EP1, EP2, and EP4 receptor mRNAs and proteins, and an EP3 receptor subtype were detected. IL-1β treatment (24-h) significantly decreased EP1 receptor levels; INDO abrogated this down-regulation. FP, EP2, and EP4 receptor levels increased after IL-1β and IL-1β + INDO. A selective FP agonist, cloprostenol (0.1 μM), and PGF (10 μM) had similar effects on IL-1β mRNA levels in progenitors treated with IL-1β + INDO. None of the EP2/EP4 agonists [butaprost, misoprostol, or 11-deoxy PGEx (10 μM)] affected IL-1β mRNA levels. In contrast, EP1/EP3 agonists (17-phenyl trinor PGE2 and sulprostone) increased IL-1β mRNAs in a dose-dependent manner. EP1 receptor subtype-selective antagonist, SC-51322, blocked IL-1β-induced and [IL-1β + INDO + 17-phenyl trinor PGE2]-induced increases in IL-1β mRNAs. Taken together, our data demonstrate that FP and EP1 receptors mediate PGF and PGE2 induction of progenitor IL-1β expression.