Mifepristone(RU486)Inducing Abortion in a Mouse Model by Regulating Innate and Adaptive Immune Responses
Mifepristone(RU486)Inducing Abortion in a Mouse Model by Regulating Innate and Adaptive Immune Responses
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米非司酮 (RU486) 通过调节先天和适应性免疫反应诱导小鼠流产
DOI：
10.4103/2096-2924.288021
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发表时间：
2020
影响因子：
0.8
通讯作者：
Du Meirong
中科院分区：
文献类型：
--
作者：
Li Mengdie;Sang Yifei;Tang Yunhui;Xu Ling;Xu Chunfang;Li Dajin;Li Yanhong;Zhang Jianping;Du Meirong
目的：米非司酮（Mifepristone，RU 486）是最常用的人工流产药物之一，它可减弱孕酮的免疫调节作用，但RU 486在人工流产中的免疫调节机制尚不清楚，本研究旨在探讨RU 486对人工流产的免疫调节作用。将60只雌性小鼠分为对照组（0 mg RU 486）和RU 486组获得子宫、外周血和脾脏用于分离特定细胞类型。使用流式细胞术分析蜕膜、外周血和脾脏中免疫细胞的群体和表型。使用双尾t检验确定组间的统计学差异。对于所有统计学检验，结果：RU 486能有效诱导孕鼠流产，蜕膜巨噬细胞（dMφ）数量明显增加，但与对照组相比差异无统计学意义（P> 0.05）。对照组为25.55% ± 2.467%，RU 486组为19.41% ± 1.423%; RU 486诱导流产小鼠的dMφ在脾脏和外周血中的表达无明显变化，且呈明显的活化表型，与对照组相比差异有显著性（P <0.05）。RU 486组蜕膜组织中诱导型一氧化氮合酶、肿瘤坏死因子-α、白细胞介素（IL）-12的表达增加，而IL-1、IL-10的表达降低。RU 486组蜕膜组织中CD 4 + T细胞水平升高，促炎细胞因子γ-干扰素水平升高，抗炎细胞因子IL-4、IL-10水平降低。我们报道了RU 486诱导流产的一个新机制，即通过调节固有细胞Mφ的激活和存在于蜕膜而非外周的CD 4 ~+ T细胞的适应性反应。
Objective:Mifepristone(RU486),one of the most common medications for artificial abortion,attenuates the immunoregulatory effects of progesterone.However,the specific immune regulatory mechanism of RU486 in abortion remains unknown.We intended to investigate the immunomodulatory effects of RU486 on abortion.Methods:Sixty female mice were divided into the control group(0 mg RU486)and RU486 group(2 mg/kg RU486).The uterus,peripheral blood,and spleen were obtained for isolation of specific cell types.The population and phenotype of immune cells in the decidua,peripheral blood,and spleen were analyzed using flow cytometry.Statistical differences between groups were determined using two-tailed t-test.For all statistical tests,P <0.05 was considered statistically significant.Results:RU486 effectively induced abortion in pregnant mice,with a significantly higher number of decidual macrophages(dMφ)(control group = 25.55% ± 2.467%,RU486 group = 19.41% ± 1.423%;P <0.05),especially the major histocompatibility complex IIhigh subset.No difference in Mφ number was observed in the spleen or peripheral blood.Moreover,the dMφ from mice with RU486-induced abortion displayed a remarkable activated phenotype,with increased expressions of inducible nitric oxide synthase,tumor necrosis factor-α,and interleukin(IL)-12 but decreased expressions of arginase-1 and IL-10.We also found elevated levels of decidual CD4~+ T-cells in the RU486 group that exhibited a higher level of the proinflammatory cytokine interferon-γ and a lower level of the anti-inflammatory cytokines,IL-4 and IL-10.Conclusions:We report a new mechanism of RU486-induced abortion via the regulation of innate cell Mφ activation and the adaptive response of CD4~+ T-cells present in the decidua but not the periphery.