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Prostaglandin E 2 (PGE 2) is an inflammatory mediator involved in the pathogenesis of several chronic inflammatory conditions, including endometritis. Previous studies have shown that PGE 2 accumulates in Escherichia coli -challenged ex vivo endometrial explants, increasing the expression of pro-inflammatory factors and aggravating tissue damage; these alterations are linked to key enzymes involved in the synthesis of PGE 2 , including cyclooxygenases-2 (COX-2) and microsomal PGES-1 (mPGES-1). In this study, we aimed to investigate whether administration of PGE 2 modulated the activities of nitric oxide synthase 2 (NOS2), platelet-activating factor receptor (PAFR), and matrix metalloproteinase (MMP)-2 in E. coli- challenged ex vivo bovine endometrial explants. Our findings showed that COX-2 and mPGES-1 inhibitors significantly reduced NOS2, PAFR, and MMP-2 expression in the E. coli -challenged ex vivo endometrial explants. In addition, NOS2, PAFR, and MMP-2 expression levels were strongly increased in response to treatment with 15-prostaglandin dehydrogenase inhibitors in the E. coli- challenged ex vivo endometrial explants. However, these stimulatory effects could be blocked by PGE 2 receptor 4 (EP4) and protein kinase A (PKA) inhibitors. Overall, these findings show that pathogenic PGE 2 upregulated NOS2, PAFR, and MMP-2 expression, which may enhance inflammatory damage via the EP4/PKA signaling pathway in E. coli- challenged ex vivo endometrial explants. • Pathogenic bacteria (E. coli) infected bovine endometrial tissue in vitro. • PGE 2 promotes NOS2, PAFR, and MMP-2 expression in E. coli -infected bovine endometrial tissues in vitro. • PGE 2 promotes NOS2, PAFR, and MMP-2 expression via the prostaglandin E 2 receptor 4/protein kinase A signaling pathway. [ABSTRACT FROM AUTHOR]

• NLRP3 engaged in the secretion of inflammatory mediators after E. coli treatment. • NLRP3 engaged in the activation of MAPK and NF-κB signaling-pathway. • NLRP3 engaged in caspase1 signaling-pathway activation after E. coli treatment. • NLRP3 contributes to liver damage in mice after E. coli infection. The host Toll-like Receptor-2 (TLR2) and Toll-like Receptor-4 (TLR4) play critical roles in defense against Escherichia coli (E. coli) infection is well-known. The NLR pyrin domain-containing 3 (NLRP3) inflammasome is also an important candidate during the host-recognized pathogen, while the roles of NLRP3 in the host inflammatory response to E. coli infection remains unclear. This study aimed to explore the roles of NLRP3 in regulating the inflammatory response in E. coli infection-induced mice. Our result indicated that compared to wild-type mice, the TLR2-deficient (TLR2-/-), TLR4-deficient (TLR4-/-), and NLRP3-deficient (NLRP3-/-) mice had significant decrease in liver damage after stimulation with Lipopolysaccharide (LPS, 1 μg/mL), Braun lipoprotein (BLP, 1 μg/mL), or infected by WT E. coli (1 × 107 CFU, MOI 5:1). Meanwhile, compared with wild-type mice, the TNF-α and IL-1β production in serum decreased in TLR2-/-, TLR4-/-, and NLRP3-/- mice after LPS, BLP treatment, or WT E. coli infection. In macrophages from NLRP3-/- mice showed significantly reduced secretion of TNF-α and IL-1β in response to stimulation with LPS, BLP, or WT E. coli infection compared with macrophages from wild-type mice. These results indicate that besides TLR2 and TLR4, NLRP3 also plays a critical role in host inflammatory responses to defense against E. coli infection, and might provide a therapeutic target in combating disease with bacterium infection. [ABSTRACT FROM AUTHOR]