title: Particulate matter 2.5 induces autophagy via inhibition of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin kinase signaling pathway in human bronchial epithelial cells.
abstract: Particulate matter 2.5 (PM2.5) is a significant risk factor for asthma. A recent study revealed that autophagy was associated with asthma pathogenesis. However, the specific mechanisms underlying PM2.5-induced autophagy in asthma have remained elusive. In the present study, PM2.5-induced autophagy was evaluated in Beas-2B human bronchial epithelial cells and the potential molecular mechanisms were investigated. Using electron microscopy, immunofluorescence staining and immunoblot studies, it was confirmed that PM2.5 induced autophagy in Beas-2B cells as a result of PM2.5-mediated inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in Beas-2B cells. LY294002, a PI3K inhibitor, reduced the accumulation of microtubule-associated protein 1 light chain 3 II and attenuated the effect of PM2.5. Phosphorylated (p-)p38, p-extracellular signal-regulated kinase and p-c-Jun N-terminal kinase were dephosphorylated following exposure to PM2.5. The roles of p53, reactive oxygen species scavenger tetramethylthiourea and autophagy inhibitor 3-methyladenine in PM2.5-induced autophagy in Beas-2B cells were also investigated. The results suggested that the PI3K/Akt/mTOR signaling pathway may be a key contributor to PM2.5-induced autophagy in Beas-2B cells. The results of the present study therefore provided an a insight into potential future clinical applications targeting these signaling pathways, for the prevention and/or treatment of PM2.5-induced lung diseases.
authors.affiliation: Clinical Research Center, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Tie
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Clinical Research Center, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Yahong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Clinical Research Center, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: He
authors.affiliation: Clinical Research Center, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Ziying
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Clinical Research Center, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Tan
authors.affiliation: Clinical Research Center, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Lawei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine and Jesse Brown VA Medical Center, Chicago, IL 60611, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Kamp
authors.affiliation: Clinical Research Center, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Clinical Research Center, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Tang
authors.affiliation: Clinical Research Center, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Haili
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Immunology and Tumor Research Institute, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
authors.forename: Liangqing
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Clinical Research Center, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Liu
authors.initials: L
authors.lastname: Bin
authors.affiliation: Clinical Research Center, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D001343:Autophagy / Q000187:drug effects*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008171:Lung Diseases / Q000139:chemically induced / Q000209:etiology; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
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