ROS Generated by Upconversion Nanoparticle-Mediated Photodynamic Therapy Induces Autophagy Via PI3K/AKT/mTOR Signaling Pathway in M1 Peritoneal Macrophage (Retracted Article)
ROS Generated by Upconversion Nanoparticle-Mediated Photodynamic Therapy Induces Autophagy Via PI3K/AKT/mTOR Signaling Pathway in M1 Peritoneal Macrophage (Retracted Article)
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DOI：
10.1159/000492283
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Yang, Liming
中科院分区：
文献类型：
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作者：
Han, Xiaobo;Zhong, Zhaoyu;Yang, Liming
背景/目的：动脉粥样硬化是一种慢性炎症性心血管疾病。巨噬细胞是动脉粥样硬化斑块的主要组成部分，通过分泌多种促炎因子在动脉粥样硬化的发展过程中发挥关键作用。我们以前的研究证实，包裹氯素e6(UCNPS-Ce6)的上转换纳米颗粒(UCNPS-Ce6)介导的光动力疗法(PDT)可以促进THP-1巨噬细胞的胆固醇外流和诱导凋亡。在这项研究中，我们研究了UCNPS-Ce6介导的PDT产生的活性氧物种(ROS)是否可以诱导自噬来抑制M1腹膜巨噬细胞中促炎因子的表达。方法：取C57/BL6小鼠腹腔巨噬细胞，用3%硫代乙醇酸盐肉汤接种，用脂多糖和干扰素-γ诱导。用2‘-7’-二氯氟苯二乙酸酯和流式细胞仪检测细胞内ROS的产生。免疫印迹、透射电子显微镜和免疫荧光检测细胞自噬。采用酶联免疫吸附试验和免疫印迹法检测促炎细胞因子的表达。结果：诱导后24 h即可建立M1模型小鼠腹腔巨噬细胞模型。PDT组Lc3 II和Beclin1蛋白表达增加，p62降解增加，2 h达高峰。同时，炎症细胞因子iNOS、IL-12和TNF-α水平在PDT后显著降低。3-甲基腺嘌呤可显著抑制自噬水平的升高和促炎细胞因子的降低。此外，UCNPS-Ce6介导的PDT产生的ROS激活了自噬。ROS抑制剂N-乙酰半胱氨酸可抑制自噬相关蛋白和炎性细胞因子iNOS、IL-12和TNF-α的表达。结论：UCNPS-CE6介导的PDT产生的ROS通过PI3K/AKT/mTOR信号通路激活了M1巨噬细胞的自噬并抑制了促炎因子的表达。(C)2018年作者(S)由S.Karger AG，巴塞尔出版
Background/Aims: Atherosclerosis is a chronic inflammatory cardiovascular disease. Macrophages are major components of atherosclerotic plaques and play a key role in the development of atherosclerosis by secreting a variety of pro-inflammatory factors. Our previous studies have confirmed that upconversion nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) mediated photodynamic therapy (PDT) can promote cholesterol efflux and induce apoptosis in THP-1 macrophages. In this study, we investigated whether reactive oxygen species (ROS) generated by UCNPs-Ce6-mediated PDT can induce autophagy to inhibit the expression of pro-inflammatory factor in M1 peritoneal macrophages. Methods: Peritoneal macrophages were collected from C57/BL6 mice injected with 3% thioglycollate broth medium and induced by lipopolysaccharides and interferon-gamma. Intracellular ROS production was assessed by 2'-7'-dichloroflorescein diacetate and flow cytometry. Autophagy was assayed by western blot, transmission electron microscopy and immunofluorescence. Pro-inflammatory cytokines were detected by enzyme-linked immunosorbent assay and western blot. Results: Model M1 peritoneal macrophages were established after 24 h induction. Protein expression levels of LC3 II and Beclin1, and degradation of p62 increased and peaked at 2 h in the PDT group. Meanwhile, levels of inflammatory cytokines iNOS, IL-12, and TNF-alpha markedly decreased after PDT. The increase in autophagy levels and decrease in pro-inflammatory cytokines were significantly inhibited by 3-methyladenine. Furthermore, ROS generated by UCNPs-Ce6 mediated PDT activated autophagy. The expression of autophagy related-protein and inflammatory cytokines iNOS, IL-12, and TNF-alpha were inhibited by the ROS inhibitor N-acetyl cysteine. Conclusions: ROS generated by UCNPs-Ce6-mediated PDT activated autophagy and inhibited the expression of pro-inflammatory factors of M1 peritoneal macrophage via the PI3K/ AKT/mTOR signaling pathway. (c) 2018 The Author(s) Published by S. Karger AG, Basel