Xu Xu-Chen, Wu Yin-Fang, Zhou Jie-Sen, Chen Hai-Pin, Wang Yong, Li Zhou-Yang, Zhao Yun, Shen Hua-Hao, Chen Zhi-Hua
Department of Respiratory and Critical Care Medicine, Second Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Respiratory and Critical Care Medicine, Second Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; State Key Lab of Respiratory Disease, Guangzhou, China.
Toxicol Lett. 2017 Oct 5;280:206-212. doi: 10.1016/j.toxlet.2017.08.081. Epub 2017 Sep 1.
Particulate matter (PM) is a significant risk factor for airway injury. We have recently demonstrated a pivotal role of autophagy in mediating PM-induced airway injury. In the present study, we examined the possible effects of autophagy inhibitors spautin-1 and 3-Methyladenine (3-MA) in protection of PM-induced inflammatory responses. We observed that PM triggered autophagy in human bronchial epithelial (HBE) cells and in mouse airways. Spautin-1 or 3-MA inhibited PM-induced expression of inflammatory cytokines in HBE cells, and decreased the neutrophil influx and proinflammatory cytokines induced by PM in vivo. We further illustrated that autophagy inhibitors suppressed the inflammation responses via inhibition of the nuclear factor-кB (NF-кB) pathway. Thus, this study shows a paradigm that autophagy inhibitors effectively decrease the PM-induced airway inflammation via suppressing the NF-кB pathway, which may provide novel preventive and/or protective approaches for PM-related airway injury.
颗粒物(PM)是气道损伤的一个重要风险因素。我们最近证明了自噬在介导PM诱导的气道损伤中起关键作用。在本研究中,我们研究了自噬抑制剂spautin-1和3-甲基腺嘌呤(3-MA)对PM诱导的炎症反应的可能保护作用。我们观察到PM在人支气管上皮(HBE)细胞和小鼠气道中引发自噬。Spautin-1或3-MA抑制了HBE细胞中PM诱导的炎症细胞因子表达,并减少了体内PM诱导的中性粒细胞流入和促炎细胞因子。我们进一步证明自噬抑制剂通过抑制核因子-кB(NF-кB)途径抑制炎症反应。因此,本研究表明了一种模式,即自噬抑制剂通过抑制NF-кB途径有效降低PM诱导的气道炎症,这可能为PM相关气道损伤提供新的预防和/或保护方法。