Lipopolysaccharide stimulates bovine endometrium explants through toll?like receptor 4 signaling and PGE2 synthesis

Lipopolysaccharide stimulates bovine endometrium explants through toll?like receptor 4 signaling and PGE2 synthesis
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脂多糖通过 Toll 样受体 4 信号传导和 PGE2 合成刺激牛子宫内膜外植体

DOI:
10.1016/j.plefa.2021.102272
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发表时间:
2021-04-22
影响因子:
3
通讯作者:
Mao, Wei
Mao, Wei
中科院分区:
医学4区
文献类型:
--
作者:
Deng, Yang;Liu, Bo;Mao, Wei

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牛子宫内膜革兰氏阴性菌感染通常引起子宫疾病。先前的研究表明,前列腺素 E2 (PGE2) 是细菌性子宫内膜炎的炎症介质。然而,脂多糖(LPS)诱导牛子宫内膜外植体炎症反应调节的机制仍不清楚。在本研究中,在 LPS 刺激之前,用 15-羟基前列腺素脱氢酶 (15-PGDH) 抑制剂对牛外植体进行预处理。评估了 PGE2 分泌、前列腺素合成酶、促炎因子、损伤相关分子模式 (DAMP) 和相关信号通路因子水平。使用 15-PGDH 抑制剂预处理,LPS 处理的牛子宫内膜外植体表现出 PGE2 和 DAMP 表达增强,以及各种信号通路因子的上调。在预处理的子宫内膜外植体中诱导蛋白激酶 A (PKA)、细胞外信号调节激酶和 c-Jun N 末端激酶磷酸化和核转录因子-κB (NF-κB) 抑制剂的降解。 LPS 诱导的 PGE2 积累通过牛外植体中的 Toll 样受体 4 信号传导作为促炎介质,其机制可能涉及 PKA、丝裂原激活蛋白激酶和 NF-κB 途径。
Bovine endometrium infection with gram-negative bacteria commonly causes uterine diseases. Previous studies indicate that prostaglandin E2 (PGE2) is an inflammatory mediator in bacterial endometritis. However, the mechanism underlying lipopolysaccharide (LPS)-induced inflammatory response regulation in bovine endometrial explants remains elusive. In the present study, bovine explants were pre-treated with 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitors before LPS stimulation. PGE2 secretion, prostaglandin synthetase, proinflammatory factor, damage-associated molecular pattern (DAMP), and related signaling pathway factor levels were evaluated. Using 15-PGDH inhibitors pre-treatment, LPS-treated bovine endometrial explants exhibited augmentation of PGE2 and DAMP expression, and upregulation of various signaling pathway factors. Protein kinase A (PKA), extracellular-signal-regulated kinase, and c-Jun N-terminal kinase phosphorylation and degradation of nuclear transcription factor-?B (NF-?B) inhibitors were induced in the pre-treated endometrial explants. The mechanism underlying LPS-induced PGE2 accumulation acting as a pro-inflammatory mediator through tolllike receptor 4 signaling in bovine explants could involve the PKA, mitogen-activated protein kinase, and NF-?B pathways.