TLR2/4 promotes PGE(2) production to increase tissue damage in Escherichia coli-infected bovine endometrial explants via MyD88/p38 MAPK pathway

摘要

Prostaglandin E2 (PGE(2)), a lipid mediator, is released by several cell types including endometrial cells and plays a central role in bacterial infection of the endometrium during inflammation. PGE(2) production accumulated in Escherichia coli (E. coli)-infected bovine endometrial tissue, which increased E. coli-infected endometrial tissue damage. However, the mechanisms of PGE(2) accumulation in the E. coli-infected endometrium during inflammation-associated endometrial tissue damage remain unclear. This study was conducted to investigate the role of Toll-like receptors (TLRs) 2 and 4 in increased PGE(2) production in E. coli-infected endometrial tissue. E. coli and TLR2/4 agonists significantly induced cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression and PGE(2) synthesis detected by RT-PCR, Western blot, and ELISA in the endometrial tissue. The expression and synthesis were dramatically decreased by TLR4, myeloid differentiation factor88 (MyD88), and p38 mitogen-activated protein kinase (MAPK) inhibitors in E. coli-infected endometrial tissue. These inhibitors also significantly decreased proinflammatory factor (interleukin-6 and tumor necrosis factor-alpha) and damage-associated molecular pattern (high mobility group box-1 and hyaluronan-binding protein-1) release and tissue damage measured by double-label immunofluorescence in E. coli-infected endometrial explants. Our work provides in vitro evidence that TLR2/4-MyD88/p38 MAPK promotes PGE(2) synthesis and E. coli-infected endometrial tissue damage, which may be useful for improving PGE(2)-based therapies for endometritis. (C) 2020 Elsevier Inc. All rights reserved.