Corticotropin-Releasing Hormone (CRH) Promotes Inflammation in Human Pregnant Myometrium: The Evidence of CRH Initiating Parturition?
Corticotropin-Releasing Hormone (CRH) Promotes Inflammation in Human Pregnant Myometrium: The Evidence of CRH Initiating Parturition?
复制标题
促肾上腺皮质激素释放激素 (CRH) 促进人类妊娠子宫肌层炎症：CRH 启动分娩的证据？
DOI：
10.1210/jc.2013-3366
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发表时间：
2014-02-01
影响因子：
5.8
通讯作者：
Ni, Xin
中科院分区：
文献类型：
--
作者：
You, Xingji;Liu, Jie;Ni, Xin
背景：越来越多的证据表明，人类劳动，无论是足月还是早产，都是一种炎症事件。CRH是人类分娩的触发因素之一，目的：探讨CRH是否能诱导妊娠子宫肌层炎症级联反应，从而激活子宫。用Multiplex和ELISA法测定细胞因子和前列腺素（PGs）的产量。结果：足月分娩组子宫组织中趋化因子、细胞因子及活化的核因子-κ B（NF-κ B）水平均高于未足月分娩组，差异有统计学意义（P < 0. 05）。CRH刺激培养的子宫平滑肌细胞（USMCs）产生大量趋化因子和细胞因子，诱导单核细胞的趋化性。这些作用由CRH受体1（CRHR 1）介导，并依赖于腺苷酸环化酶/蛋白激酶（PKA）和NF-κ B信号传导。CRH处理的USMCs与单核细胞的共培养大大提高了细胞因子和趋化因子以及培养物中PG的输出，并增加了USMCs中子宫活化蛋白（UAPs）的表达。IL-1 β、IL-6和TNF-α刺激UAPs的表达和PGs在USMCs.Conclusions中的输出：CRH诱导子宫肌层中的趋化因子和细胞因子的产生，随后导致子宫炎症级联反应。CRH引起的炎症反应可导致子宫活动。
Context: An increasing body of evidence indicates that human labor, either term or preterm, is an inflammatory event. CRH has been implicated to be a trigger of human parturition.Objective: To investigate whether CRH induces the cascades of inflammation in human pregnant myometrium, thereby leading to activation of uterus.Design: The myometrial tissues were obtained from pregnant women who were in labor or not in labor at term. The output of cytokines and prostaglandins (PGs) was determined by Multiplex and ELISA. Western blot analysis was used to determine the levels of uterine activation proteins (UAPs).Results: The levels of chemokines and cytokines as well as activated nuclear factor-kappa B (NF-kappa B) were increased in the term labor group more than the not term labor group. CRH stimulated production of a number of chemokines and cytokines in cultured uterine smooth muscle cells (USMCs), which induced chemotaxis of monocytes. These effects were mediated by CRH receptor 1 (CRHR1) and dependent on adenylyl cyclase/protein kinase (PKA) and NF-kappa B signaling. Cocultures of CRH-treated USMCs with monocytes greatly enhanced the output of cytokines and chemokines as well as PGs in cultures and increased the expression of uterine activation proteins (UAPs) in USMCs. IL-1 beta, IL-6, and TNF-alpha stimulated the expression of UAPs and output of PGs in USMCs.Conclusions: CRH induces the production of chemokines and cytokines in myometrium at term and subsequently results in the cascade of inflammation in uterus. The inflammation induced by CRH can lead to activation of uterus.