Preeclampsia-related increase of interleukin-11 expression in human decidual cells
Preeclampsia-related increase of interleukin-11 expression in human decidual cells
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DOI：
10.1530/rep-10-0263
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发表时间：
2010-10-01
期刊：
影响因子：
3.8
通讯作者：
Kayisli, Umit A.
中科院分区：
文献类型：
--
作者：
Basar, Murat;Yen, Chih-Feng;Kayisli, Umit A.
先兆子痫与全身炎症增加和浅表滋养层侵袭有关，从而导致子宫胎盘血流不足。白细胞介素 (IL)-11 介导促炎和抗炎过程并促进蜕膜化。为了鉴定先兆子痫和对照样本中母体-胎盘界面处的 IL11 体内表达，并评估子痫前期升高的肿瘤坏死因子-α (TNF) 和 IL1B（先兆子痫中升高的细胞因子）对体外妊娠早期蜕膜细胞中 IL11 水平的调节作用，对胎盘切片进行了 IL11 免疫染色。将无白细胞的妊娠早期蜕膜细胞与雌二醇 (E-2) +/- 10(-7) mol/l 醋酸甲羟孕酮 +/- TNF 或 IL1B +/- p38 MAP 激酶 (p38 MAPK)、核因子 kappa B (NFKB) 或蛋白激酶 C (PKC) 信号通路抑制剂一起孵育。 ELISA 评估分泌的 IL11 水平，定量 RT-PCR 测量 IL11 mRNA。与胎龄匹配的对照相比，子痫前期蜕膜细胞的胎盘切片中的 IL11 免疫反应性显着较高。与蜕膜细胞相比，邻近滋养层中的 IL11 免疫染色较低，位于血管周围，并且在对照和先兆子痫标本之间没有差异。 TNF 和 IL1B 增强培养的蜕膜细胞中 IL11 mRNA 的水平并分泌 IL11。 p38 MAPK 和 NFKB 的特异性抑制剂（而非 PKC 信号通路）降低了 IL1B 的刺激作用。先兆子痫中蜕膜 IL11 的表达增加，表明 IL11 在先兆子痫的发病机制中发挥作用。复制（2010）140 605-612
Preeclampsia is associated with increased systemic inflammation and superficial trophoblast invasion, which leads to insufficient uteroplacental blood flow. Interleukin (IL)-11 mediates pro-and anti-inflammatory processes and facilitates decidualization. To identify IL11 expression in vivo at the maternal-placental interface in preeclampsia and control specimens and to evaluate the regulatory effects of tumor necrosis factor-alpha (TNF) and IL1B, cytokines elevated in preeclampsia, on IL11 levels in first trimester decidual cells in vitro, placental sections were immunostained for IL11. Leukocyte-free first trimester decidual cells were incubated with estradiol (E-2) +/- 10(-7) mol/l medroxyprogesterone acetate +/- TNF or IL1B +/- inhibitors of the p38 MAP kinase (p38 MAPK), nuclear factor-kappa B (NFKB), or protein kinase C (PKC) signaling pathways. An ELISA assessed secreted IL11 levels, and quantitative RT-PCR measured IL11 mRNA. IL11 immunoreactivity in placental sections was significantly higher in the cytoplasm of preeclamptic decidual cells versus gestational age-matched controls. Compared to decidual cells, IL11 immunostaining in neighboring trophoblast is lower, perivascular, and not different between control and preeclamptic specimens. TNF and IL1B enhanced levels of IL11 mRNA and secreted IL11 in cultured decidual cells. Specific inhibitors of the p38 MAPK and NFKB, but not PKC signaling pathways, reduced the stimulatory effect of IL1B. Expression of decidual IL11 is increased in preeclampsia and suggests a role for IL11 in the pathogenesis of preeclampsia. Reproduction (2010) 140 605-612