PGE2 downregulates LPS-induced inflammatory responses via the TLR4-NF-κB signaling pathway in bovine endometrial epithelial cells
PGE2 downregulates LPS-induced inflammatory responses via the TLR4-NF-κB signaling pathway in bovine endometrial epithelial cells
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DOI：
10.1016/j.plefa.2018.01.004
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发表时间：
2018-02-01
影响因子：
3
通讯作者：
Cao, Jinshan
中科院分区：
文献类型：
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作者：
Shen, Yuan;Liu, Bo;Cao, Jinshan
产后子宫细菌感染引起奶牛子宫炎。对牛子宫中细菌感染的炎症反应是通过模式识别受体（PRRs）产生的，PRRs与病原体相关分子（如大肠杆菌的脂多糖（LPS））结合。在这些PRR中，Toll样受体4（TLR 4）主要负责LPS识别，其通过促分裂原活化蛋白激酶（MAPK）和NF-κ B信号传导活化触发炎症反应，导致哺乳动物中炎症介质如IL-8和IL-6的表达。先前的研究表明，PGE（2）在细菌性子宫内膜炎中起着重要的作用，尽管关于它如何调节牛子宫内膜上皮细胞（bEECs）中LPS诱导的炎症反应的机制的细节仍然难以捉摸。在本研究中，在LPS刺激之前用外源性PGE（2）和/或PGF（2 α）预处理bEEC。我们观察到前列腺素E（2）预处理可增加bEEC中LPS刺激的PKA、ERK和I κ B α磷酸化以及环氧合酶-2（考克斯-2）和抗炎细胞因子IL-6的表达，并下调前列腺素E-2受体4（EP 4）和TLR 4。这些结果表明，外源性PGE（2）预处理可下调bEEC中通过TLR 4信号传导的LPS诱导的炎症反应，但PGF（2 α）不能下调。
Postpartum bacterial infections of the uterus cause endometritis in dairy cows. Inflammatory responses to bacterial infections in the bovine uterus were generated through pattern recognition receptors (PRRs) that bind to pathogen-associated molecules such as lipopolysaccharide (LPS) from Escherichia coli. Among these PRRs, Toll-like receptor 4 (TLR4) is primarily responsible for LPS recognition, which triggers inflammatory responses via mitogen-activated protein kinases (MAPKs) and NF-kappa B signaling activation, resulting in the expression of inflammatory mediators in mammals such as IL-8 and IL-6. Previous studies indicate that PGE(2) plays an important role in bacterial endometritis, although details on the mechanism underlying how it regulates LPS-induced inflammatory responses in bovine endometrial epithelial cells (bEECs) remain elusive. In the present study, bEECs were pre-treated with exogenous PGE(2) and/or PGF(2 alpha) prior to LPS stimulation. With PGE(2) pretreatment, we observed an augmentation in LPS-stimulated PKA, ERK, and I kappa B alpha phosphorylation and cyclooxygenase-2 (COX-2) and anti-inflammatory cytokine IL-6 expression and downregulation of prostaglandin E-2 receptor 4 (EP4) and TLR4 in bEECs. These results indicate that LPS-induced inflammatory responses through TLR4 signaling in bEECs could be downregulated by exogenous PGE(2) pre-treatment, but not PGF(2 alpha).