RT Journal Article
SR Electronic
T1 EP2/4 Receptors Promote the Synthesis of PGE<sub>2</sub> Increasing Tissue Damage in Bovine Endometrial Explants Induced by <em>Escherichia coli</em>
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 175
OP 184
DO 10.1124/jpet.119.262444
VO 372
IS 2
A1 Chao Zhang
A1 Lingrui Wang
A1 Tingting Li
A1 Wei Mao
A1 Bo Liu
A1 Jinshan Cao
YR 2020
UL http://jpet.aspetjournals.org/content/372/2/175.abstract
AB The bovine uterine is easily contaminated with bacteria during coitus or parturition. A previous study suggested that prostaglandin E2 (PGE2) promoted Escherichia coli–infected bovine endometrial tissue inflammatory damage via cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1). However, it remains unclear which PGE2 receptors regulate the proinflammatory effect of PGE2. In this study, we evaluated the effect of PGE2 and its mediated receptors on E. coli–infected endometrium explants isolated from the bovine uterus. The E. coli–infected bovine endometrial explants were cultured in vitro, and the study used EP2/4 receptor agonists to investigate the responses of COX-2, mPGES-1, PGE2, proinflammatory factors, and damage-associated molecular patterns (DAMPs). The expression of COX-2, mPGES-1, PGE2, proinflammatory factors, and DAMPs was significantly increased after infection with E. coli; however, the high expression levels caused by E. coli were reduced following treatment with COX-2 and mPGES-1 inhibitors. In addition, the expression levels of COX-2, mPGES-1, PGE2, proinflammatory factors, and DAMPs were higher in treatment with EP2/4 receptor agonists in E. coli–infected endometrium explants, and their promotable effects were effectively blocked by EP2/4 receptor antagonists. These findings provide evidence that PGE2 may promote the progress of inflammation in endometrial explants infected with E. coli in bovines. Furthermore, EP2/4 may be involved in a positive feedback loop for COX-2 and mPGES-1 expression, and this may be responsible for the proinflammatory reaction of PGE2 in E. coli–infected uteri of bovines.SIGNIFICANCE STATEMENT PGE2 promoted E. coli–infected bovine endometrial tissue damage via COX-2 and mPGES-1. However, this proinflammatory effect of PGE2 depends on which receptors are affected by PGE2, and this remains unclear. In this study, it was investigated that EP2 and EP4 may be involved in a positive feedback loop for COX-2 and mPGES-1 expression, and this may be responsible for the proinflammatory reaction of PGE2 in E. coli–infected uteri of bovines.