1. Prostaglandin E2 promotes nitric oxide synthase 2, platelet-activating factor receptor, and matrix metalloproteinase-2 expression in Escherichia coli-challenged ex vivo endometrial explants via the prostaglandin E2 receptor 4/protein kinase a signaling pathway
- Author
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Li, Tingting, Liu, Bo, Mao, Wei, Gao, Ruifeng, Wu, Jindi, Deng, Yang, Shen, Yuan, Liu, Kun, and Cao, Jinshan
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PROSTAGLANDIN receptors , *DINOPROSTONE , *NITRIC-oxide synthases , *ESCHERICHIA , *INFLAMMATORY mediators , *PROTEIN kinases - Abstract
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]
- Published
- 2019
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