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

Abstract

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 STATEMENTPGE 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.

LPS Mediates Bovine Endometrial Epithelial Cell Pyroptosis Directly Through Both NLRP3 Classical and Non-Classical Inflammasome Pathways

“…The inflammatory environment is increased in the bovine uterus due to bacterial contamination and tissue degradation driven by local pathogenassociated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Post-parturition inflammation has been described as a normal physiological event, indicating that the bovine uterus needs proper tissue remodeling to restore its homeostasis for future pregnancy (3,4). Although, most cows try to eliminate bacterial contamination in the uterus during post parturient through the uterine mucosal immune response, about half of postpartum cows still develop endometritis (5), which has a high incidence of disease in postpartum cows worldwide.…”

Role of Noradrenaline and Adrenoreceptors in Regulating Prostaglandin E2 Synthesis Cascade in Inflamed Endometrium of Pigs

“…It has been established that PGE2 reduces the contractile amplitude and frequency of both kinds of uterine strips (endometrium with myometrium, myometrium alone) of the E. coli -infected uteri [ 19 ]. It is known that in bovine endometrial explants affected by LPS or E. coli , PGE2 production was increased via PTGS-2 and mPTGES-1, which led to the expression and secretion of pro-inflammatory mediators and damage-associated molecular patterns [ 17 , 18 ]. Pro-inflammatory cytokines (tumor necrosis factor α, interferon-γ) and leukotrienes (B4, C4) also led to the elevation in PGE2 release from the E. coli -treated cow uterine explants [ 52 ].…”

“…PGE2, as a very important inflammatory mediator, plays a role in many processes leading to the classic signs of an inflammatory state [ 16 ]. In the cow endometrium, PGE2 increased the production and release of other pro-inflammatory mediators and damage-associated molecular patterns [ 17 , 18 ]. The role of this PG in the control of inflamed pig uterus contractility was also presented [ 19 ].…”

Codonopsis pilosula polysaccharides attenuate Escherichia coli-induced acute lung injury in mice

“…A reported pathogenic E. coli wild-type (WT) strain (identification certificate number: SYS110017) was stored in our lab. 30 To determine the number of colony-forming units (CFU) in the bacterial suspension used in this study, 1 mL of bacterial sus-pension (1 × 10 7 CFU) was seeded in 100 mL of Luria-Bertani (LB; Oxoid, Basingstoke, UK) broth and incubated with shaking at 37 °C for 12 h (with OD 600 nm of value approximately 0.9 in the log phase). Thereafter, the cultured bacterial suspension was serially diluted and plated on LB agar plates with incubation at 37 °C for 12 h. The colony counting technique was used for determining the total number of CFU (approximately 1 × 10 8 CFU mL −1 ).…”