Autophagy inhibitors suppress environmental particulate matter-induced airway inflammation

被引:23
|
作者
Xu, Xu-Chen [1 ]
Wu, Yin-Fang [1 ]
Zhou, Jie-Sen [1 ]
Chen, Hai-Pin [1 ]
Wang, Yong [1 ]
Li, Zhou-Yang [1 ]
Zhao, Yun [1 ]
Shen, Hua-Hao [1 ,2 ]
Chen, Zhi-Hua [1 ]
机构
[1] Zhejiang Univ, Sch Med, Hosp 2, Dept Resp & Crit Care Med, Hangzhou, Zhejiang, Peoples R China
[2] State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Particulate matter; Airway injury; Autophagy inhibitors; EPITHELIAL-CELLS; DNA-DAMAGE; KAPPA-B; ACTIVATION; EXPOSURE; PATHWAYS; DEATH; FINE;
D O I
10.1016/j.toxlet.2017.08.081
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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-kappa B (NF-kappa B) pathway. Thus, this study shows a paradigm that autophagy inhibitors effectively decrease the PM-induced airway inflammation via suppressing the NF-kappa B pathway, which may provide novel preventive and/or protective approaches for PM-related airway injury.
引用
收藏
页码:206 / 212
页数:7
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