Lipoxin A4 Suppresses IL-1β-Induced Cyclooxygenase-2 Expression Through Inhibition of p38 MAPK Activation in Endometriosis:

Endometriosis 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...