芳香烃受体和 NOD 样受体家族成员 3 的高表达将多环芳烃暴露与学龄前儿童细胞因子风暴联系起来。
Elevated expression of AhR and NLRP3 link polycyclic aromatic hydrocarbon exposure to cytokine storm in preschool children.
机构信息
Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands.
Laboratory of Environmental Medicine and Developmental Toxicology, Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou 511443, Guangdong, China.
出版信息
Environ Int. 2020 Jun;139:105720. doi: 10.1016/j.envint.2020.105720. Epub 2020 Apr 11.
BACKGROUND
Polycyclic aromatic hydrocarbons (PAHs), as a group of persistent organic pollutants, are linked to impaired immune function and low-grade inflammation in adults and children. However, the potential of PAHs to lead to a cytokine storm associated with AhR (aryl hydrocarbon receptor) and NLRP3 (NLR family pyrin domain containing 3) in humans has been poorly studied.
OBJECTIVES
We aimed to investigate the associations between PAH exposure, AhR and NLRP3 expression, and cytokines associated with a cytokine storm in healthy preschoolers.
METHODS
Basic demographic surveys and physical examinations were conducted on 248 preschoolers from an electronic waste (e-waste) recycling area (Guiyu, n = 121) and a reference area (Haojiang, n = 127). Ten urinary PAH metabolite (OH-PAH) concentrations were measured. We also measured the expression levels of AhR and NLRP3 and seventeen serum cytokine levels.
RESULTS
The concentrations of multiple OH-PAHs were significantly higher in the exposed group than those in the reference group, especially 1-hydroxynaphthalene (1-OH-Nap) and 2-hydroxynaphthalene (2-OH-Nap). PAH exposure was closely related to a child's living environment and hygiene habits. Expression levels of AhR and NLRP3 were significantly higher in the exposed group than in the reference group. Similarly, serum IL-1β, IL-4, IL-5, IL-10, IL-12p70, IL-13, IL-17A, IL-18, IL-22, IL-23, and IFN-γ levels were notably higher in the e-waste-exposed children than in the reference children. After adjusting for age, gender, BMI, family income, parental education level, and second-hand smoke exposure, we found that increased PAH exposure was associated with higher AhR and NLRP3 expression and elevated IL-4, IL-10, IL-12p70, IL-18, IL-22, IL-23, TNF-α, and IFN-γ levels. The associations between PAH exposure and IL-1β, IL-18, IFN-γ, and TNF-β were mediated by NLRP3 expression, and the relationships between PAH exposure and IL-4, IL-10, IL-12p70, IL-22, IL-23, and TNF-α were mediated by AhR expression.
CONCLUSIONS
Our findings suggest that the association between PAH exposure and a cytokine storm may be mediated by AhR and NLRP3 expression among preschoolers.
背景
多环芳烃（PAHs）作为一组持久性有机污染物，与成年人和儿童的免疫功能受损和低度炎症有关。然而，PAHs 导致与 AhR（芳烃受体）和 NLRP3（含pyrin 结构域的 NLR 家族蛋白 3）相关的细胞因子风暴的潜力在人类中研究甚少。
目的
本研究旨在探讨 PAH 暴露、AhR 和 NLRP3 表达与健康学龄前儿童细胞因子风暴相关的细胞因子之间的关系。
方法
对来自电子废物（e-waste）回收区（贵屿，n=121）和对照区（濠江，n=127）的 248 名学龄前儿童进行基本人口统计学调查和体格检查。测量了 10 种尿多环芳烃代谢物（OH-PAH）浓度。我们还测量了 AhR 和 NLRP3 的表达水平以及 17 种血清细胞因子水平。
结果
暴露组中多种 OH-PAH 浓度明显高于对照组，尤其是 1-羟基萘（1-OH-Nap）和 2-羟基萘（2-OH-Nap）。PAH 暴露与儿童的生活环境和卫生习惯密切相关。暴露组 AhR 和 NLRP3 的表达水平明显高于对照组。同样，暴露于电子废物的儿童血清中 IL-1β、IL-4、IL-5、IL-10、IL-12p70、IL-13、IL-17A、IL-18、IL-22、IL-23 和 IFN-γ 水平明显高于对照组。在调整年龄、性别、BMI、家庭收入、父母教育水平和二手烟暴露后，我们发现，PAH 暴露增加与 AhR 和 NLRP3 表达增加以及 IL-4、IL-10、IL-12p70、IL-18、IL-22、IL-23、TNF-α和 IFN-γ 水平升高有关。PAH 暴露与 IL-1β、IL-18、IFN-γ 和 TNF-β之间的关系通过 NLRP3 表达介导，而 PAH 暴露与 IL-4、IL-10、IL-12p70、IL-22、IL-23 和 TNF-α之间的关系通过 AhR 表达介导。
结论
本研究结果表明，学龄前儿童中，PAH 暴露与细胞因子风暴之间的关联可能通过 AhR 和 NLRP3 表达介导。
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