A role for IL-17 in induction of an inflammation at the fetomaternal interface in preterm labour

被引:100
作者
Ito, Mika [1 ]
Nakashima, Akitoshi [1 ]
Hidaka, Takao [1 ]
Okabe, Motonori [2 ]
Bac, Nguyen Duy [3 ,4 ]
Ina, Shihomi [1 ]
Yoneda, Satoshi [1 ]
Shiozaki, Arihiro [1 ]
Sumi, Shigeki [5 ]
Tsuneyama, Koichi [6 ]
Nikaido, Toshio [2 ]
Saito, Shigeru [1 ]
机构
[1] Toyama Univ, Dept Obstet & Gynecol, Toyama 9300194, Japan
[2] Toyama Univ, Dept Regenerat Med, Toyama 9300194, Japan
[3] Vietnam Mil Med Univ, Dept Anat, Hatay, Vietnam
[4] Vietnam Mil Med Univ, Dept Genom & Cytogenet, Hatay, Vietnam
[5] Toyama Univ, Div Biostat & Clin Epidemiol, Ctr Advancement Med Training, Toyama 9300194, Japan
[6] Toyama Univ, Dept Diagnost Pathol, Toyama 9300194, Japan
关键词
Amniotic fluid; Chorioamnionitis; IKK; MAPK; Preterm delivery; Th17; TUMOR-NECROSIS-FACTOR; FACTOR-KAPPA-B; AMNIOTIC-FLUID; T-CELLS; HISTOLOGIC CHORIOAMNIONITIS; CYTOKINE LEVELS; FACTOR-ALPHA; MAP-KINASE; INFECTION; EXPRESSION;
D O I
10.1016/j.jri.2009.09.005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:75 / 85
页数:11
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