Luteal fibroblasts produce prostaglandins in response to IL1β in a MAPK-mediated manner

• Published in: Molecular and cellular endocrinology 2025-01, Vol.596, p.112420, Article 112420
• Main Authors: Monaco, Corrine F., Jones, Chloe M., Sayles, Harlan R., Rudloff, Brooke, McFee, Renee, Cupp, Andrea S., Davis, John S.
• Format: Article
• Language: English
• Subjects: Animals; Cattle; Cells, Cultured; Corpus luteum; Corpus Luteum - drug effects; Corpus Luteum - metabolism; Cyclooxygenase 2 - metabolism; Cytokine; Dinoprostone - metabolism; Female; Fibroblast; Fibroblasts - drug effects; Fibroblasts - metabolism; Interleukin; Interleukin-1beta - metabolism; Interleukin-1beta - pharmacology; MAP Kinase Signaling System - drug effects; Microenvironment; Phospholipases A2, Cytosolic - metabolism; Phosphorylation - drug effects; Prostaglandins; Prostaglandins - metabolism; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0303-7207; 1872-8057; 1872-8057
• DOI: 10.1016/j.mce.2024.112420

The corpus luteum is a temporary endocrine gland that is crucial for pregnancy, as it produces the progesterone needed to maintain optimal uterine conditions for implantation. In the absence of a conceptus, the corpus luteum becomes non-functional and undergoes rapid tissue remodeling to regress into a fibrotic corpus albicans. Early luteal regression is characterized by increased cytokine release. Because the role of fibroblasts in the bovine corpus luteum remains to be elucidated, the aim of this study was to elucidate the response of bovine luteal fibroblasts to inflammatory cytokines, tumor necrosis factor α (TNFα), and interleukin 1β (IL1β). Both cytokines induced canonical mitogen activated protein kinase (MAPK) signaling in luteal fibroblasts by phosphorylation of ERK1/2, p38 MAPK, and JNK. IL1β elevated expression and phosphorylation of cytosolic phospholipase A2 (cPLA2), an enzyme that mobilizes arachidonic acid for prostanoid synthesis. IL1β also elevated expression of prostaglandin-endoperoxide synthase 2 (PTGS2), another enzyme needed to synthesize prostanoids. IL1β increased PGF2α and PGE2 levels in the culture medium over 20-fold. Inhibition of MAPKs with small-molecule inhibitors abrogated the stimulatory effects of IL1β. IL1β also induced prostaglandin production in steroidogenic cells; however, there was no elevation in cPLA2. Therefore, actions of IL1β differ based on ovarian cell type. All together, we have identified luteal fibroblasts as potential inflammatory mediators during luteal regression. [Display omitted] •Bovine luteal fibroblasts are responsive to the inflammatory cytokines IL1β and TNFα.•IL1β, but not TNFα, increases luteal fibroblast production of PGF2α and PGE2.•IL1β elevates cPLA2 in luteal fibroblasts but not in steroidogenic cells.•Bovine luteal fibroblasts contribute lipid mediators to the microenvironment during luteal regression.