在哮喘模型中，PM2.5通过释放中性粒细胞胞外诱捕网加剧NQO1诱导的黏液过度分泌。
PM2.5 aggravates NQO1-induced mucus hyper-secretion through release of neutrophil extracellular traps in an asthma model.
作者信息
He Xiang, Zhang Lei, Xiong Anying, Ran Qin, Wang Junyi, Wu Dehong, Niu Bin, Liu Shengbin, Li Guoping
机构信息
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.
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.
出版信息
Ecotoxicol Environ Saf. 2021 May 4;218:112272. doi: 10.1016/j.ecoenv.2021.112272.
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.
背景
直径2.5微米及以下的颗粒物（PM2.5）是大气环境中最复杂的污染物之一，对人体健康有害。流行病学证据表明，哮喘发作与接触PM2.5有关。然而，PM2.5在哮喘发展中的分子机制尚未完全阐明。
方法
收集中国成都的PM2.5并分析其成分。在卵清蛋白（OVA）诱导的哮喘小鼠模型中研究PM2.5暴露与哮喘严重程度之间的关系。分析来自公共数据库的U-BIOPRED数据和我们自己的RNA测序数据以鉴定枢纽基因。在体外和体内研究中应用实时定量PCR、免疫荧光、免疫组织化学和病理染色进行机制剖析。
结果
在PM2.5样本中，共鉴定出包括常量元素和微量元素在内的11种元素，16种多环芳烃（PAHs）中除苊和芴外检测到14种。PM2.5暴露加重了哮喘模型中的肺部炎症、黏液分泌和中性粒细胞浸润。基于对轻度至重度哮喘数据集的转录组分析，结果显示黏液分泌和中性粒细胞脱颗粒与哮喘严重程度相关。此外，通过联合分析筛选出NAD(P)H：醌氧化还原酶1（NQO1）作为枢纽基因，其表达与哮喘患者的MUC5AC表达呈正相关。此外，在OVA诱导的哮喘模型和体外试验中，还揭示了PM2.5诱导的MU5AC表达受NQO1通过氧化应激引起的中性粒细胞胞外陷阱（NETs）调节。
结论
综上所述，我们发现了哮喘严重程度与PM2.5暴露之间的潜在关系。此外，中性粒细胞耗竭、NETs抑制或抗NQO1可能是治疗PM2.5诱导的黏液过度分泌的新型潜在治疗选择。
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