抑制巨噬细胞产生促炎性因子对异位内膜孕酮反应的影响
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江苏省“333”工程(LGY2016003);江苏省妇幼健康项目(F201619);江苏省妇幼健康重点人才(FRC201709)


Amending of progesterone resistance in ectopic endometrial stromal cells via NF⁃κB decoy oligonucleotides⁃mediated inhibition of pro⁃inflammatory cytokine production from LPS⁃triggered macrophages
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    摘要:

    目的:探讨抑制巨噬细胞产生促炎性细胞因子对子宫内膜异位症孕酮拮抗的影响。方法:原代培养15例异位子宫内膜基质细胞(endometrial stromal cells,ESCs),趋化实验检测异位ESCs表达的趋化因子配体12(CXCL12)对巨噬细胞的趋化能力。脂质体法介导核因子(nuclear factor,NF)-κB诱捕寡核苷酸(oligonucleotide,ODNs)转染巨噬细胞后再用100 ng/mL脂多糖刺激培养巨噬细胞,电泳迁移率分析(electrophoretic mobility shift assay,EMSA)法检测脂多糖刺激条件下巨噬细胞中NF-κB的活化水平,ELISA检测巨噬细胞白介素-1β(interleukin-1β,IL-1β)和肿瘤坏死因子-α(tumor necrosis factor α,TNF-α)表达水平的变化。建立异位ESCs和巨噬细胞的共培养系统,检测通过NF-κB诱捕ODNs抑制巨噬细胞表达促炎性细胞因子对异位ESCs蜕膜化的影响。结果:异位ESCs分泌的CXCL12对巨噬细胞具有趋化作用。NF-κB诱捕ODNs能显著抑制脂多糖诱导的巨噬细胞表达促炎性细胞因子。在巨噬细胞和异位ESCs的共培养系统中,NF-κB诱捕ODNs能通过抑制巨噬细胞产生促炎性因子提高异位ESCs对孕酮的反应。结论:通过NF-κB诱捕ODNs抑制巨噬细胞产生促炎性细胞因子有可能是减轻内异症炎症反应和改善孕酮抵抗的一种方法。

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    Objective:To investigate the effect of inhibition of proinflammatory cytokines produced by macrophages on the progesterone resistance in endometriosis. Methods:The primary ectopic endometrial stromal cells(ESCs)of 15 endometriosis women were cultured. The chemotactic test was used to detect the role of CXCL12 expressed by ectopic ESCs in the recruitment of macrophages. LPS(100 ng/mL)was used to stimulate macrophages to express pro-inflammatory cytokines after macrophages were transfected with nuclear factor(NF)-κB decoy oligonucleotides(ODNs). The electrophoretic mobility shift assay(EMSA)assay was used to detect the activation of NF-κB in macrophages after LPS stimulation,and ELISA was used to detect the expression of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in macrophages. In the co-culture system of ectopic ESCs and macrophages,the effect of NF-κB decoy ODNs on the decidualization of ectopic ESCs was observed. Results:CXCL12 secreted by ectopic ESCs played a role in the recruitment of macrophages in endometriosis. NF-κB decoy ODNs significantly inhibited the expression of pro-inflammatory cytokines in macrophages. In co-culture system of macrophages and ectopic ESCs,NF-κB decoy ODNs enhanced the progesterone-induced decidualization of ectopic ESCs by inhibiting the production of pro-inflammatory cytokines from macrophages. Conclusion:This study indicates that NF-κB targeting therapy of macrophages maybe an opportunity for mitigating the inflammatory response and progesterone resistance in endometriosis.

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李林翰,林明娟,钱欢欢,徐 炜,朱 姝,戴辉华,王秀丽.抑制巨噬细胞产生促炎性因子对异位内膜孕酮反应的影响[J].南京医科大学学报(自然科学版),2018,(7):966-972

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  • 收稿日期:2018-02-24
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  • 在线发布日期: 2018-07-20
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