IL-11 regulates the biosynthesis of PGE2 through JAK1/STAT3 signaling pathway in bovine granulosa cells

Ovulation is a highly organized and multifaceted series of events, which parallels with inflammatory processes. Prostaglandins (PGs) have been shown to play an important role in the modulation of ovulation. Our previous study revealed that Interleukin 11 (IL-11) signaling is critical in regulating steroidogenesis in bovine granulosa cells (GCs). However, the precise roles of IL-11 in the regulation of PGs remain unclear. In the present study, we investigated the effects and underlying molecular mechanisms of IL-11 on the production of PGs in primary bovine GCs. At LH-induced levels, we observed that 10 ng/mL IL-11 significantly increased prostaglandin E2 (PGE2) production via upregulating the expression of prostaglandin-endoperoxide synthase 2 (PTGS2), while IL-11 treatment did not affect the production of prostaglandin F2α (PGF2α). Furthermore, 10 ng/mL IL-11 treatment activated the phosphorylation of Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3), which was accompanied by STAT3 nuclear translocation. Additionally, these effects were inhibited by the addition of the STAT3-specific inhibitor C188-9. Specifically, C188-9 treatment blocked the IL-11-induced STAT3 nuclear translocation, downregulated the mRNA and protein expression levels of PTGS2, and ultimately led to a reduction in PGE2 production induced by 10 ng/mL IL-11. Our findings elucidate the cellular and molecular mechanisms by which IL-11 regulates PGE2 expression through the JAK1/STAT3 signaling pathway in bovine GCs in the presence of LH, contributing to a better understanding of the ovulatory process.