Elevated expression of AhR and NLRP3 link polycyclic aromatic hydrocarbon exposure to cytokine storm in preschool children
Elevated expression of AhR and NLRP3 link polycyclic aromatic hydrocarbon exposure to cytokine storm in preschool children
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AhR 和 NLRP3 表达升高与学龄前儿童多环芳烃暴露于细胞因子风暴有关
DOI：
10.1016/j.envint.2020.105720
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发表时间：
2020-06-01
影响因子：
11.8
通讯作者：
Xu, Xijin
中科院分区：
文献类型：
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作者：
Cheng, Zhiheng;Huo, Xia;Xu, Xijin
背景：多环芳烃（PAH）作为一组持久性有机污染物，与成人和儿童的免疫功能受损和轻度炎症有关。然而，PAHs在人类中导致与AhR（芳烃受体）和NLRP3（NLR家族pyrin结构域3）相关的细胞因子风暴的可能性尚未得到充分研究。目的：我们旨在研究健康学龄前儿童PAH暴露、AhR和NLRP3表达以及与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）的248名学龄前儿童进行基础人口调查和体检回收区（贵屿，n = 121）和参考区（濠江，n = 127）。测量了十种尿多环芳烃代谢物 (OH-PAH) 浓度。我们还检测了AhR和NLRP3的表达水平以及17种血清细胞因子的水平。结果：暴露组中多种OH-PAHs的浓度显着高于参考组，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。暴露组中 AhR 和 NLRP3 的表达水平显着高于参考组。同样，电子垃圾暴露儿童的血清 IL-1β、IL-4、IL-5、IL-10、IL-12p70、IL-13、IL-17A、IL-18、IL-22、IL-23 和 IFN-α 水平显着高于参考儿童。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表达升高以及IL-4、IL-10、IL-12p70、IL-18、IL-22、IL-23、TNF-α和IFN-gamma水平升高相关。 PAH 暴露与 IL-1 beta、IL-18、IFN-gamma 和 TNF-beta 之间的关联是由 NLRP3 表达介导的，PAH 暴露与 IL-4、IL-10、IL-12p70、IL-22、IL-23 和 TNF-α 之间的关系是由 AhR 表达介导的。 结论：我们的研究结果表明，PAH 暴露与细胞因子风暴之间的关联可能是由 AhR 和 NLRP3 介导的学龄前儿童的表达。
Background: Polycyclic aromatic hydrocarbons (PAHs), as a group of persistent organic pollutants, are linked to impaired immune function and low-grade in flammation 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 signi ficantly 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 signi ficantly higher in the exposed group than in the reference group. Similarly, serum IL-1 beta, IL-4, IL-5, IL-10, IL-12p70, IL-13, IL-17A, IL-18, IL-22, IL-23, and IFN-alpha 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-alpha, and IFN-gamma levels. The associations between PAH exposure and IL-1 beta, IL-18, IFN-gamma, and TNF-beta were mediated by NLRP3 expression, and the relationships between PAH exposure and IL-4, IL-10, IL-12p70, IL-22, IL-23, and TNF-alpha 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.