title: Particulate matter exposure induces the autophagy of macrophages via oxidative stress-mediated PI3K/AKT/mTOR pathway.
abstract: Many epidemiological investigations have consistently demonstrated the immunotoxicity of fine particulate matter (PM2.5), but the underlying molecular mechanism remains unclear and needs to be elucidated. In this work, the immune cells, including pulmonary macrophages of SD rats and Raw264.7 cells, were applied to further investigate the effect of PM2.5on cell autophagy of macrophages, thus clarified the possible molecular mechanism of immunotoxicity caused by PM2.5. SD rats were exposed to summer (0.2, 0.6, 1.5 mg kg-1b.w.) and winter (0.3, 1.5, 2.7 mg kg-1b.w.) PM2.5adopting the intratracheal instillation method. The exposure was performed one time every 3 days and continued for 2 months. The data showed that PM2.5exposure decreased numbers of immune cells in pulmonary macrophages of SD rats. In addition, PM2.5could induce the cell autophagy through the increased LC3 and decreased p62 mRNA and protein levels of pulmonary macrophages in SD rats and Raw264.7 cells in a concentration-dependent manner. Strikingly, PM2.5-induced oxidative stress was observed. However, NAC supplement (the ROS inhibitor) significantly reversed PM2.5-caused effects. Additionally, the PI3K/AKT/mTOR pathway was activated in PM2.5-treated cells and NAC had an important inhibitory effect. These results demonstrated that PM2.5exposures induced autophagy of pulmonary macrophages via the oxidative stress-mediated PI3K/AKT/mTOR pathway, which may contribute to explain the molecular mechanism of immunotoxicity caused by PM2.5and provide the theoretical foundation for environment toxicology of PM2.5.
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Wucheng Rood 92, Taiyuan 030006, China.
authors.forename: Ruijun
authors.initials: R
authors.lastname: Su
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Wucheng Rood 92, Taiyuan 030006, China; The Institutes of Biomedical Sciences, Shanxi University, Taiyuan 030006, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Weifang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Wucheng Rood 92, Taiyuan 030006, China. Electronic address: lzy@sxu.edu.cn.
authors.forename: Zhuoyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Wucheng Rood 92, Taiyuan 030006, China.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Medicine, Shanxi Province Staff Medical College, Jinzhong 030619, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: Autophagy; Oxidative stress; PI3K/AKT/mTOR pathway; PM(2.5); Pulmonary macrophage