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

Xiang He; Lei Zhang; Anying Xiong; Qin Ran; Junyi Wang; Dehong Wu; Bin Niu; Shengbin Liu; Guoping Li

Ecotoxicology and Environmental Safety (Jul 2021)

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

Xiang He,
Lei Zhang,
Anying Xiong,
Qin Ran,
Junyi Wang,
Dehong Wu,
Bin Niu,
Shengbin Liu,
Guoping Li

Affiliations

Xiang He: Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, the Third People’s Hospital of Chengdu, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu third people’s hospital branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Sichuan friendship hospital, Chengdu 610000, China
Lei Zhang: Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, the Third People’s Hospital of Chengdu, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu third people’s hospital branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China
Anying Xiong: Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, the Third People’s Hospital of Chengdu, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu third people’s hospital branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China
Qin Ran: Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, the Third People’s Hospital of Chengdu, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu third people’s hospital branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China
Junyi Wang: Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, the Third People’s Hospital of Chengdu, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu third people’s hospital branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China
Dehong Wu: Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, the Third People’s Hospital of Chengdu, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu third people’s hospital branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China
Bin Niu: Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, the Third People’s Hospital of Chengdu, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu third people’s hospital branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China
Shengbin Liu: Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, the Third People’s Hospital of Chengdu, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu third people’s hospital branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China
Guoping Li: Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, the Third People’s Hospital of Chengdu, Chengdu 610031, China; Department of Pulmonary and Critical Care Medicine, Chengdu third people’s hospital branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China; Corresponding author at: Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, the Third People’s Hospital of Chengdu, Chengdu 610031, China.

Journal volume & issue: Vol. 218
p. 112272

Abstract

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Background: Particulate matter of 2.5 µm 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.

Published in Ecotoxicology and Environmental Safety

ISSN: 0147-6513 (Print); 1090-2414 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Technology: Environmental technology. Sanitary engineering: Environmental pollution; Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/ecotoxicology-and-environmental-safety

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