Effect of hypothermia combined with PM2.5 on airway inflammation in asthmatic mice
FU Shi-hua1, ZHOU Ji2, YE Xiao-fang2, YANG Dan-dan2, YANG Si-xu2
1. Institute of Occupational Health and Environmental Health, School of Public Health, Lanzhou University, Lanzhou 730000, China; 2. Shanghai Key Laboratory of Meteorology and Health, Shanghai Meteorological Bureau, Shanghai 200030, China
Abstract：To explore the mechanism of cold stress and PM2.5 exposure exacerbating airway inflammation of asthma. Asthma model mice were randomly divided into control group, cold stress group, PM2.5 group and combined exposure group (n=8), and treated with the corresponding exposure environment for 4weeks. The concentration of inflammatory factors Interleukin (IL)-4, IL-6, IL-13, IL-17, transforming growth factor-β (TGF-β), and oxidation indexes such as malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were detected. The relative expressions of retinoid-related orphan nuclear receptor (RORγt) and fork-head box protein (Foxp3) were detected by PCR. The changes of T helper-17cells (Th17) and regulatory cells (Treg) were analyzed by flow cytometry. The infiltration of inflammatory cells in the bronchi in the combined exposure group was the most obvious. Compared with control group, the levels of IL-6, IL-17 and TGF-β in other three groups were higher, while the level of CAT was lower, and the combined exposure group had the most significant effect. The proportion of Th17 cells was the highest and the proportion of Treg cells was the lowest in combined exposure group. The level of RORγt in combined exposure group was significantly higher than that in cold stress group and PM2.5 group. The interaction test showed that cold stress and PM2.5 had significant interactive effects on the increase of IL-4, IL-13, IL-17, MDA and RORγt. Co-exposure of cold stress plus PM2.5 may exacerbate pulmonary inflammation by promoting the expression of RORγt and polarizing Th17/Treg.
付世华, 周骥, 叶晓芳, 杨丹丹, 杨丝絮. 低温联合PM2.5对小鼠哮喘气道炎症的影响[J]. 中国环境科学, 2021, 41(7): 3343-3348.
FU Shi-hua, ZHOU Ji, YE Xiao-fang, YANG Dan-dan, YANG Si-xu. Effect of hypothermia combined with PM2.5 on airway inflammation in asthmatic mice. CHINA ENVIRONMENTAL SCIENCECE, 2021, 41(7): 3343-3348.
Papi A, Brightling C, Pedersen S E, et al. Asthma[J]. Lancet, 2018,391(10122):783-800.
Hekking P P, Wener R R, Amelink M, et al. The prevalence of severe refractory asthma[J]. Journal of Allergy and Clinical Immunology, 2015,135(4):896-902.
Oliveira M, Slezakova K, Delerue-Matos C, et al. Children environmental exposure to particulate matter and polycyclic aromatic hydrocarbons and biomonitoring in school environments:A review on indoor and outdoor exposure levels, major sources and health impacts[J]. Environment International, 2019,124:180-204.
鲁娴娴,黄佳伟,崔海燕,等.低浓度甲醛和PM2.5联合暴露对哮喘小鼠的影响[J]. 中国环境科学, 2020,40(3):1335-1344. Lu X X, Huang J W, Cui H Y, et al. The effect of combined exposure of low concentration formaldehyde and PM2.5 on asthma model mice[J]. China Environmental Science, 2020,40(3):1335-1344.
Sun L, Fu J, Lin S H, et al. Particulate matter of 2.5μm or less in diameter disturbs the balance of T(H)17/regulatory T cells by targeting glutamate oxaloacetate transaminase 1and hypoxia-inducible factor 1α in an asthma model[J]. Journal of Allergy and Clinical Immunology, 2020,145(1):402-414.
Silverpil E, Lindén A. IL-17in human asthma[J]. Expert Review of Respiratory Medicine, 2012,6(2):173-186.
Chesné J, Braza F, Mahay G, et al. IL-17in severe asthma. Where do we stand?[J]. American Journal of Respiratory and Critical Care Medicine, 2014,190(10):1094-1101.
Evasovic J M, Singer C A. Regulation of IL-17A and implications for TGF-β1comodulation of airway smooth muscle remodeling in severe asthma[J]. American Journal of Physiology. Lung Cellular and Molecular Physiology, 2019,316(5):L843-L868.
郑钰涵,吴晓东,孙兵.Th17细胞分化和功能的研究进展[J]. 生命科学, 2010,22(6):534-538. Zheng Y H, Wu X D, Sun B. The progress on differentiation and function of Th17Cells[J]. Chinese Bulletin of Life Sciences, 2010, 22(6):534-538.
龚雨新,于化鹏,邓火金,等.Th17细胞在哮喘小鼠发病中的作用机制研究[J]. 解放军医学杂志, 2009,34(1):72-75. Gong Y X, Yu H P, Deng H J, et al. Mechanism of the role Th17cells in pathogenesis of asthmatic attact[J]. Medical Journal of Chinese People's Liberation Army, 2009,34(1):72-75.
Stelmaszczyk-Emmel A, Zawadzka-Krajewska A, Szypowska A, et al. Frequency and activation of CD4+CD25FoxP3+ regulatory T cells in peripheral blood from children with atopic allergy[J]. International Archives of Allergy and Immunology, 2013,162(1):16-24.
Nadeau K, Mcdonald-Hyman C, Noth E M, et al. Ambient air pollution impairs regulatory T-cell function in asthma[J]. Journal of Allergy and Clinical Immunology, 2010,126(4):845-852.
付慧聪,陆小霞,韩锋,等.和厚朴酚对PM2.5暴露哮喘小鼠免疫应答加剧的抑制作用[J]. 中华微生物学和免疫学杂志, 2017,37(11):827-833. Fu H C, Lu X X, Han F, et al. The inhibitory effect of honokiol on the intensified immune response of asthmatic mice exposed to PM2.5[J]. Chinese Journal of Microbiology and Immunology, 2017,37(11):827-833.
杨凌,马琼锦,李莉珊,等.PM2.5亚慢性染毒对小鼠肺部炎症及Th17/Treg的影响[J]. 卫生研究, 2014,43(3):387-392. Yang L, Ma Q J, Li L S, et al. Effects of airborne fine particulate matters on pulmonary inflammation injury and Th17/Treg balance of sub-chronic exposure mice[J]. Journal of Hygiene Research, 2014, 43(3):387-392.
赵会超,王静,吴红燕,等.交通相关PM2.5及其不同成分对哮喘大鼠Th17细胞和相关细胞因子的影响[J]. 环境与职业医学, 2019,36(5):438-444. Zhao H C, Wang J, Wu H Y, et al. Effects of traffic-related PM2.5 and its different components on Th17cells and related cytokines in asthmatic rats[J]. Journal of Environmental & Occupational Medicine, 2019,36(5):438-444.
Deng L, Ma P, Wu Y, et al. High and low temperatures aggravate airway inflammation of asthma:Evidence in a mouse model[J]. Environmental Pollution, 2020,256:113433.
Du C, Kang J, Yu W, et al. Repeated exposure to temperature variation exacerbates airway inflammation through TRPA1in a mouse model of asthma[J]. Respirology, 2019,24(3):238-245.
郭维丽,李敏超.冷刺激敏感哮喘患者的临床及炎症表型特点[J]. 南方医科大学学报, 2019,39(2):181-185. Guo W L, Li M C. Clinical and inflammatory phenotypic features of asthmatic patients sensitive to cold stimulation[J]. Journal of Southern Medical University, 2019,39(02):181-185.
Mohr L B, Luo S, Mathias E, et al. Influence of season and temperature on the relationship of elemental carbon air pollution to pediatric asthma emergency room visits[J]. The Journal of asthma:official journal of the Association for the Care of Asthma, 2008, 45(10):936-943.
Zhou J, Geng F, Xu J, et al. PM2.5 exposure and cold stress exacerbates asthma in mice by increasing histone acetylation in IL-4gene promoter in CD4(+) T cells[J]. Toxicology Letters, 2019,316:147-153.
张凯,费高强,李兴杰,等.高温及低温时大气PM2.5对大鼠肺泡巨噬细胞的毒性作用[J]. 环境与健康杂志, 2017,34(5):394-397. Zhang K, Fei G Q, Li X J, et al. Toxic effects of ambient PM2.5 exposure on rat alveolar macrophage under highand low temperature[J]. Journal of Environment and Health, 2017,34(5):394-397.
Zhang X, Zhong W, Meng Q, et al. Ambient PM2.5 exposure exacerbates severity of allergic asthma in previously sensitized mice[J]. Journal of Asthma, 2015,52(8):785-794.
Cho Y S, Lee J, Lee T H, et al. Alpha-Lipoic acid inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma[J]. Journal of Allergy and Clinical Immunology, 2004,114(2):429-435.
Li Y, Zhou J, Rui X, et al. PM2.5 exposure exacerbates allergic rhinitis in mice by increasing DNA methylation in the IFN-γ gene promoter in CD4+T cells via the ERK-DNMT pathway[J]. Toxicology Letters, 2019,301:98-107.
Wu S, Deng F, Hao Y, et al. Fine particulate matter, temperature, and lung function in healthy adults:Findings from the HVNR study[J]. Chemosphere, 2014,108:168-174.
Sun S, Cao P, Chan K P, et al. Temperature as a modifier of the effects of fine particulate matter on acute mortality in Hong Kong[J]. Environmental Pollution, 2015,205:357-364.
张莹,王式功,贾旭伟,等.气温与PM2.5协同作用对疾病急诊就诊人数的影响[J]. 中国环境科学, 2017,37(8):3175-3182. Zhang Y, Wang S G, Jia X W, et al. Synergetic effect of mean temperature and PM2.5 on emergency room visits for different diseases[J]. China Environmental Science, 2017,37(8):3175-3182.
张莹,辛金元,张小玲,等.北京市气温与黑碳和PM2.5对疾病死亡影响的交互效应[J]. 中国环境科学, 2020,40(7):3179-3187. Zhang Y, Xin J Y, Zhang X L, et al. Interaction effects between ambient temperature and black carbon and PM2.5 on mortality in Beijing[J]. China Environmental Science, 2020,40(7):3179-3187.
Luo B, Shi H, Wang L, et al. Rat lung response to PM2.5 exposure under different cold stresses[J]. International Journal of Environmental Research and Public Health, 2014,11(12):12915-12926.
罗斌,刘江涛,费高强,等.不同温度刺激与大气PM2.5对大鼠肺泡巨噬细胞的交互毒性作用研究[J]. 中国应用生理学杂志, 2017, 33(1):71-75. Luo B, Liu J T, Fei G Q, et al. Impact of different temperatures and ambient PM2.5 on the cytotoxicityand cytophagocytic function of alveolar macrophages of rat[J]. Chinese Journal of Applied Physiology, 2017,33(1):71-75.
罗斌,晚亚雄,石艳荣,等.低温刺激与PM2.5对大鼠肺组织及系统炎症因子的影响[J]. 科学技术与工程, 2015,15(7):30-33. Luo B, Wan Y X, Shi Y R, et al. The effect of low temperature stimulation and PM2.5on inflammatory factors in rat lung tissue and system[J]. Science Technology and Engineering, 2015,15(7):30-33.
Kimura A, Kishimoto T. IL-6:Regulator of Treg/Th17balance[J]. European Journal of Immunology, 2010,40(7):1830-1835.
Poole J A, Gleason A M, Bauer C, et al. Αβ T cells and a mixed Th1/Th17response are important in organic dust-induced airway disease[J]. Annals of Allergy, Asthma & Immunology:Official Publication of the American, 2012,109(4):266-273.