{"paper_id":"30fb087d-3dfd-426e-8267-2d4a32ddc324","body_text":"Abstract\nEndometriosis is an inflammation-dependent gynecologic disorder. Increased cyclooxygenase-2 (COX-2) expression plays an important role in the development and progression of endometriosis. Lipoxin A4 (LXA4) is an endogenous anti-inflammation lipid and showed inhibitory effects on the development of endometriosis; however, the mechanism remains unclear. In this study, the overexpression of COX-2 was observed in ectopic endometrium of endometriosis patients compared to the normal endometrium of controls. Lipoxin A4 efficiently suppressed IL-1β-induced COX-2 protein expression in ectopic endometriotic stromal cells (ESCs) via its receptor, formyl peptide receptor 2/lipoxin A4 receptor (FPR2/ALX). Antagonism of FPR2/ALX eliminated the inhibitory effect by LXA4. IL-1β induced the activation of mitogen-activated protein kinases (MAPKs), which can promote the expression of COX-2. Pretreatment of ESCs with LXA4 inhibited the phosphorylation of p38 MAPK induced by IL-1β. These findings suggest that inflammation and MAPKs pathways respond for the abnormal expression of COX-2, which can elucidate the pathophysiology of endometriosis. Moreover, LXA4 suppressed IL-1β-induced COX-2 expression through inhibiting the p38 MAPK signaling protein. This research contributes for better understanding of the cellular and biological events of inflammation and anti-inflammation-mediated regulation in endometriosis.\nSimilar content being viewed by others\nReferences\nGiudice LC, Kao LC. Endometriosis. Lancet (London, England). 2004;364(9447):1789–1799.\nTakenaka Y, Taniguchi F, Miyakoda H, Takai E, Terakawa N, Harada T. Lipopolysaccharide promoted proliferation and invasion of endometriotic stromal cells via induction of cyclooxygenase-2 expression. Fertil steril. 2010;93(1):325–327.\nBinion DG, Otterson MF, Rafiee P. 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Int JClin Exp Pathol. 2013;6(10):2129–2136.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nSupplemental Material\nSupplemental Material\nSupplemental material for this article is available online.\nRights and permissions\nAbout this article\nCite this article\nDai, S., Zhu, M., Wu, R. et al. Lipoxin A4 Suppresses IL-1β-Induced Cyclooxygenase-2 Expression Through Inhibition of p38 MAPk Activation in Endometriosis. Reprod. Sci. 26, 1640–1649 (2019). https://doi.org/10.1177/1933719119828115\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1177/1933719119828115","source_license":"CC0","license_restricted":false}