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The bovine uterine is easily contaminated with bacteria during coitus or parturition. A previous study suggested that prostaglandin E 2 (PGE 2 ) 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 PGE 2 receptors regulate the proinflammatory effect of PGE 2 In this study, we evaluated the effect of PGE 2 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, PGE 2 , proinflammatory factors, and damage-associated molecular patterns (DAMPs). The expression of COX-2, mPGES-1, PGE 2 , 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, PGE 2 , 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 PGE 2 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 PGE 2 in E. coli -infected uteri of bovines. SIGNIFICANCE STATEMENT: PGE 2 promoted E. coli -infected bovine endometrial tissue damage via COX-2 and mPGES-1. However, this proinflammatory effect of PGE 2 depends on which receptors are affected by PGE 2 , 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 PGE 2 in E. coli -infected uteri of bovines.

EP2/4 Receptors Promote the Synthesis of PGE2Increasing Tissue Damage in Bovine Endometrial Explants Induced byEscherichia coli

EP2/4 Receptors Promote the Synthesis of PGE₂Increasing Tissue Damage in Bovine Endometrial Explants Induced byEscherichia coli