Prostaglandin E2 receptor 3 promotes M1 macrophages polarization in unexplained recurrent pregnancy loss
Prostaglandin E2 receptor 3 promotes M1 macrophages polarization in unexplained recurrent pregnancy loss
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前列腺素 E2 受体 3 促进不明原因复发性流产中 M1 巨噬细胞极化
DOI：
10.1093/biolre/ioac030
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发表时间：
2022-02
影响因子：
3.6
通讯作者：
Viktoria von Schönfeldt
中科院分区：
文献类型：
--
作者：
Yao Ye;Lin Peng;Anca Chelariu-Raicu;Christina Kuhn;Xi Dong;Udo Jeschke;Viktoria von Schönfeldt
原因不明的反复妊娠丢失（uRPL）与巨噬细胞极化有关，这可以通过前列腺素E2（PGE 2）调节。我们以前的研究表明，PGE 2受体3（EP 3）信号被诱导的前三个月的uRPL患者的胎盘相比，其表达在健康对照组。然而，EP 3是否在uRPL妇女的母胎界面处的巨噬细胞极化中起作用仍然未知。免疫荧光双标法检测uRPL患者和健康对照组早孕胎盘组织中EP 3的表达。抗体CD 68、iNOS和CD 163用作蜕膜巨噬细胞、M1和M2巨噬细胞的免疫荧光标记物。为了阐明EP 3对巨噬细胞极化的影响，在佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）处理后，将THP-1单核细胞用作M0巨噬细胞用于体外研究。在用硫前列酮（一种EP 3激动剂）或L-798，106（一种EP 3拮抗剂）刺激的M0巨噬细胞中，采用qPCR定量代表性M1标志物（白细胞介素-1 β和白细胞介素-6）和M2标志物（白细胞介素-10和β-内酰胺酶-1）的mRNA水平。我们发现，与健康对照组相比，EP 3的表达在URPL患者孕早期胎盘的蜕膜巨噬细胞中上调。此外，在uRPL患者的早期妊娠胎盘中，与M2巨噬细胞相比，M1巨噬细胞中的EP 3表达增加。硫前列酮与干扰素-γ一起增强IL-6的mRNA水平，而L-798，106以剂量依赖性方式刺激IL-10和Arg-1的mRNA表达。
Unexplained recurrent pregnancy loss (uRPL) is associated with macrophage polarization, which can be modulated by prostaglandin E2 (PGE2). Our previous study demonstrated that PGE2 receptor 3 (EP3) signaling is induced in the first-trimester placentas of uRPL patients compared with its expression in healthy controls. However, whether EP3 plays a role in macrophage polarization at the maternal-fetal interface of uRPL women remains unknown. The positive expression of EP3 in decidual macrophages was confirmed by double immunofluorescence staining in the first-trimester placentas collected from uRPL patients and healthy controls. Antibodies CD68, iNOS, and CD163 were used as immunofluorescence marker for decidual macrophages, M1, and M2 macrophages. To clarify the effects of EP3 on macrophage polarization, THP-1 monocyte cells were applied as M0 macrophages after phorbol 12-myristate 13-acetate (PMA) treatment for in vitro study. The mRNA levels of representative M1 markers (interleukin-1β and interleukin-6) and M2 markers (interleukin-10 and arginase-1) were quantified with qPCR in M0 macrophages being stimulated with sulprostone (an EP3 agonist) or L-798,106 (an EP3 antagonist). We found that EP3 expression was upregulated in the decidual macrophages of first-trimester placentas from uRPL patients compared with healthy controls. Furthermore, EP3 expression was increased in M1 macrophages compared with that in M2 macrophages in first-trimester placentas of uRPL patients. Sulprostone intensified the mRNA levels of IL-6 together with interferon-γ, whereas L-798,106 stimulated the mRNA expression of IL-10 and Arg-1 in a dose-dependent manner.
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影响因子：
4.4
作者：
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通讯作者：
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影响因子：
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