A role for IL-17 in induction of an inflammation at the fetomaternal interface in preterm labour
A role for IL-17 in induction of an inflammation at the fetomaternal interface in preterm labour
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DOI：
10.1016/j.jri.2009.09.005
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发表时间：
2010-01-01
影响因子：
3.4
通讯作者：
Saito, Shigeru
中科院分区：
文献类型：
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作者：
Ito, Mika;Nakashima, Akitoshi;Saito, Shigeru
绒毛膜炎（CAM）是早产的主要原因。炎性细胞因子和趋化因子在早产的发病机制中起重要作用。白细胞介素（IL）-17是一种诱导炎症的关键细胞因子，对宿主防御至关重要。在这项研究中，我们研究了IL-17在早产发病机制中的作用。采用酶联免疫吸附法（ELISA）检测154例早产孕妇羊水中IL-17、IL-8和肿瘤坏死因子（TNF）α水平。流式细胞术和免疫组织化学染色，以确定IL-17产生细胞的分布。在用IL-17、TNF α或IL-1 β刺激的原代培养的人羊膜间充质（HAM）细胞和人羊膜上皮（HAE）细胞中评价IL-8分泌。我们还研究了HAM细胞中IL-17和TNF α的信号通路。早产组羊水中炎性细胞因子水平高于足月分娩组。此外，IL-8、IL-17和TNF α水平在CAM II或III期早产病例中显著高于无CAM的早产病例。流式细胞术和免疫组化染色显示，CD 3（+）CD 4（+）T细胞是绒毛膜羊膜中IL-17的主要来源。有趣的是，在HAM细胞中，IL-17以剂量依赖性方式增强TNF α诱导的IL-8分泌。IKK抑制剂BMS-345541和丝裂原活化蛋白激酶（MAPK）抑制剂p38、JNK和p42/44（ERK 1/2途径）减少了IL-17刺激和TNF α刺激的HAM细胞的IL-8分泌。这些结果表明，由T细胞产生的IL-17在早产中促进母胎界面的炎症。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
Chorioamnionitis (CAM) is a major cause of preterm delivery. Inflammatory cytokines and chemokines play important roles in the pathogenesis of preterm delivery. Interleukin (IL)-17 is a key cytokine which induces inflammation and is critical to host defense. In this study, we examined the role of IL-17 in the pathogenesis of preterm delivery. The levels of cyrokines including IL-17, IL-8 and tumor necrosis factor (TNF) alpha were measured by ELISA in amniotic fluid from 154 cases of preterm labor. Flow cytometry and immunohistochemical staining were performed to determine the distribution of IL-17-producing cells. IL-8 secretion was evaluated in primary cultured human amniotic mesenchymal (HAM) cells and human amniotic epithelial (HAE) cells stimulated with IL-17, TNF alpha or IL-1 beta. We also studied the signaling pathway of IL-17 and TNF alpha in HAM cells. Levels of inflammatory cytokines in amniotic fluid were higher in preterm delivery cases than in term delivery cases. Furthermore, IL-8, IL-17 and TNF alpha levels were significantly higher in the preterm cases with CAM stage II or III than those without CAM. Flow cytometry and immunohistochemical staining revealed that CD3(+)CD4(+) T cells were the main source of IL-17 in the chorioamniotic membrane. Interestingly, TNF alpha-induced IL-8 secretion was enhanced by IL-17 in a dose-dependent manner in HAM cells. The IKK inhibitor BMS-345541 and mitogen-activated protein kinase (MAPK) inhibitors p38, JNK and p42/44 (ERK1/2 pathway) reduced IL-8 secretion by IL-17-stimulated and TNF alpha-stimulated HAM cells. These results indicate that IL-17, produced by T cells, promotes inflammation at the fetomaternal interface in preterm delivery. (C) 2009 Elsevier Ireland Ltd. All rights reserved.