Cellular Physiology and Biochemistry (Aug 2018)

ROS Generated by Upconversion Nanoparticle-Mediated Photodynamic Therapy Induces Autophagy Via PI3K/AKT/ mTOR Signaling Pathway in M1 Peritoneal Macrophage

  • Xiaobo Han,
  • Zhaoyu Zhong,
  • Jiayuan Kou,
  • Yinghong Zheng,
  • Zhongni Liu,
  • Yueqing Jiang,
  • Zhiren Zhang,
  • Ziyu Gao,
  • Lin Cong,
  • Ye Tian,
  • Liming Yang

DOI
https://doi.org/10.1159/000492283
Journal volume & issue
Vol. 48, no. 4
pp. 1616 – 1627

Abstract

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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-γ. Intracellular ROS production was assessed by 2’-7’-dichloroforescein 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-α 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-α 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.

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