PM2.5 aggravates NQO1-induced mucus hyper-secretion through release of neutrophil extracellular traps in an asthma model

作者全名："He, Xiang; Zhang, Lei; Xiong, Anying; Ran, Qin; Wang, Junyi; Wu, Dehong; Niu, Bin; Liu, Shengbin; Li, Guoping"

作者地址："[He, Xiang; Zhang, Lei; Xiong, Anying; Ran, Qin; Wang, Junyi; Wu, Dehong; Niu, Bin; Liu, Shengbin; Li, Guoping] Third Peoples Hosp Chengdu, Chengdu Inst Resp Hlth, Lab Allergy & Precis Med, Chengdu 610031, Peoples R China; [He, Xiang; Zhang, Lei; Xiong, Anying; Ran, Qin; Wang, Junyi; Wu, Dehong; Niu, Bin; Liu, Shengbin; Li, Guoping] ChongQing Med Univ, Chengdu Peoples Hosp Branch 3, Natl Clin Res Ctr Resp Dis, Dept Pulm & Crit Care Med,Affiliated Hosp, Chengdu 610031, Peoples R China; [He, Xiang] Sichuan Friendship Hosp, Dept Pulm & Crit Care Med, Chengdu 610000, Peoples R China"

通信作者："Li, GP (corresponding author), Third Peoples Hosp Chengdu, Chengdu Inst Resp Hlth, Lab Allergy & Precis Med, Chengdu 610031, Peoples R China."

来源：ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY

ESI学科分类：ENVIRONMENT/ECOLOGY

WOS号：WOS:000652685400003

JCR分区：Q1

影响因子：6.8

年份：2021

卷号：218

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：PM2; 5; Asthma; NETs; Mucus secretion; NQO1; MUC5AC

摘要："Background: Particulate matter of 2.5 & micro;m or less in diameter (PM2.5) is one of the most complex pollutants in the atmospheric environment and harmful to human health. Epidemiologic evidence suggests that asthma exacerbation is associated with PM2.5 exposure. However, the molecular mechanism of PM2.5 in the development of asthma is not fully addressed. Methods: PM2.5 was collected from Chengdu, China, and the components were analyzed. The relationship between PM2.5 exposure and asthma severity was investigated in an Ovalbumin (OVA)-induced murine model of asthma. U-BIOPRED data from public database and our own RNA-seq data were analyzed to identify the hub genes. Real-time qPCR, immunofluorescence, immunohistochemistry and pathological staining were applied for mechanism dissection in both in vitro and in vivo studies. Results: In PM2.5 samples, a total of 11 elements including major elements and trace elements were identified, 14 of the 16 Polycyclic aromatic hydrocarbons (PAHs) were detected except Acenaphthene and Fluorene. PM2.5 exposure aggravated pulmonary inflammation, mucus secretion, and neutrophils infiltration in asthma model. Based on transcriptome analysis of mild-to-severe asthma dataset, it showed that mucus secretion and neutrophil degranulation correlated with asthma severity. Moreover, NAD(P)H:quinone oxidoreductase 1 (NQO1) was screened out as a hub gene whose expression positively correlated with MUC5AC expression in patient with asthma by performing joint analysis. Furthermore, in OVA-induced asthma model and in vitro assay, it also revealed that PM2.5-induced MU5AC expression was regulated by NQO1 through neutrophil extracellular traps (NETs) caused by oxidative stress. Conclusion: Taken together, we discovered a potential relationship between asthma severity and PM2.5 exposure. In addition, neutrophil depletion, NETs inhibition or anti-NQO1 might be novel potential therapeutic options for treatment of PM2.5-induced mucus hyper-secretion."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81970026, 82000029]; Health Commission of Sichuan Province [19ZD002, 20PJ208, 20PJ209]; Science and Technology Department of Sichuan Province [2018JY0380]; Health Commission of Chengdu [2019078, 2019023, 2019077]; project of high level key clinical specialty in Chengdu"

基金资助正文："This work was supported by the National Natural Science Foundation of China (81970026, 82000029) , Health Commission of Sichuan Province (19ZD002, 20PJ208, 20PJ209) , Science and Technology Department of Sichuan Province (2018JY0380) , and Health Commission of Chengdu (2019078, 2019023 and 2019077) , the project of high level key clinical specialty in Chengdu."