Liu Tie, Wu Bin, Wang Yahong, He Huijuan, Lin Ziying, Tan Jianxin, Yang Lawei, Kamp David W, Zhou Xu, Tang Jinfeng, Huang Haili, Zhang Liangqing, Bin Liu, Liu Gang
Clinical Research Center, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
Department of Respiratory Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
Mol Med Rep. 2015 Aug;12(2):1914-22. doi: 10.3892/mmr.2015.3577. Epub 2015 Mar 31.
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.
细颗粒物2.5(PM2.5)是哮喘的一个重要风险因素。最近一项研究表明,自噬与哮喘发病机制有关。然而,PM2.5在哮喘中诱导自噬的具体机制仍不清楚。在本研究中,我们在人支气管上皮细胞Beas-2B中评估了PM2.5诱导的自噬,并研究了其潜在的分子机制。通过电子显微镜、免疫荧光染色和免疫印迹研究,证实PM2.5通过介导Beas-2B细胞中磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)/雷帕霉素哺乳动物靶蛋白(mTOR)信号通路的抑制,从而诱导Beas-2B细胞发生自噬。PI3K抑制剂LY294002减少了微管相关蛋白1轻链3 II的积累,并减弱了PM2.5的作用。暴露于PM2.5后,磷酸化(p-)的p38、磷酸化细胞外信号调节激酶和磷酸化c-Jun氨基末端激酶发生去磷酸化。我们还研究了p53、活性氧清除剂四甲基硫脲和自噬抑制剂3-甲基腺嘌呤在PM2.5诱导Beas-2B细胞自噬中的作用。结果表明,PI3K/Akt/mTOR信号通路可能是PM2.5诱导Beas-2B细胞自噬的关键因素。因此,本研究结果为未来针对这些信号通路进行潜在的临床应用以预防和/或治疗PM2.5诱导的肺部疾病提供了见解。