Extracellular ATP (eATP) inhibits the progression of endometriosis and enhances the immune function of macrophages
Extracellular ATP (eATP) inhibits the progression of endometriosis and enhances the immune function of macrophages
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细胞外ATP（eATP）抑制子宫内膜异位症的进展并增强巨噬细胞的免疫功能
DOI：
10.1016/j.bbadis.2023.166895
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发表时间：
2023-10-10
影响因子：
6.2
通讯作者：
Chang，Xiaohong
中科院分区：
文献类型：
--
作者：
Zhou，Ling;Cai，E.;Chang，Xiaohong
研究背景细胞外三磷酸腺苷（eATP）是一种重要的炎症介质，可增强抗肿瘤免疫反应，但其在子宫内膜异位症中的作用尚不清楚。我们假设，eATP可以抑制子宫内膜异位症细胞的功能，直接和间接通过macrophage.MethodsPeritoneal和囊肿液子宫内膜异位症患者和非子宫内膜异位症对照组收集测量eATP水平。加入eATP以探索其对增生细胞和巨噬细胞功能的影响，包括细胞增殖、凋亡、焦亡、线粒体膜电位、吞噬作用以及炎性细胞因子和活性氧的产生。建立了增生上皮细胞和U937巨噬细胞的共培养物，随后进行P2 X7拮抗剂和eATP处理。结果子宫内膜异位症患者盆腔微环境中eATP水平升高，可通过MAPK/JNK/Akt通路诱导异位上皮细胞凋亡和焦亡，并显著抑制细胞生长。eATP治疗改善了与糖尿病相关的巨噬细胞功能障碍，并促进了巨噬细胞的募集。在巨噬细胞存在的情况下，eATP处理通过调节P2 X7对增生性上皮细胞产生更强的细胞毒性作用。eATP治疗有效地诱导细胞死亡在子宫内膜异位症大鼠模型和显着增加巨噬细胞的数量，而不影响在位endometriois.ConclusioneATP诱导增生性上皮细胞死亡，增强巨噬细胞的免疫功能，抑制子宫内膜异位症的进展，而在位子宫内膜不受影响。eATP治疗可作为子宫内膜异位症的非激素治疗策略。
BackgroundExtracellular adenosine triphosphate (eATP) is an important inflammatory mediator that can boost the antitumour immune response, but its role in endometriosis remains unknown. We hypothesized that eATP could inhibit endometriosis cell function both directly and indirectly through macrophages.MethodsPeritoneal and cyst fluid from endometriosis patients and non-endometriosis controls was collected to measure eATP levels. The addition of eATP was performed to explore its effects on endometriotic cell and macrophage functions, including cell proliferation, apoptosis, pyroptosis, mitochondrial membrane potential, phagocytosis, and the production of inflammatory cytokines and reactive oxygen species. A coculture of endometriotic epithelial cells and U937 macrophages was established, followed by P2X7 antagonist and eATP treatment. Endometriosis model eATP-treated rats were used to evaluate in situ cell death and macrophage marker expression.ResultsThe pelvic microenvironment of endometriosis patients shows high eATP levels, which could induce endometriotic epithelial cell apoptosis and pyroptosis and significantly inhibit cell growth via the MAPK/JNK/Akt pathway. eATP treatment ameliorated endometriosis-related macrophage dysfunction and promoted macrophage recruitment. eATP treatment in the presence of macrophages exerted a stronger cytotoxic effect on endometriotic epithelial cells by regulating P2X7. eATP treatment effectively induced cell death in an endometriosis rat model and prominently increased the macrophage number without affecting the eutopic endometrium.ConclusioneATP induces endometriotic epithelial cell death and enhances the immune function of macrophages to inhibit the progression of endometriosis, while eutopic endometrium is not affected. eATP treatment may serve as a nonhormonal therapeutic strategy for endometriosis.