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阐明苯并三唑紫外线稳定剂在斑马鱼(Danio rerio)中的免疫毒性机制:AHR-IL17/IL22 免疫途径的影响。

Elucidating mechanisms of immunotoxicity by benzotriazole ultraviolet stabilizers in zebrafish (Danio rerio): Implication of the AHR-IL17/IL22 immune pathway.

机构信息

Inner Mongolia Key Laboratory of Environmental Pollution Control & Waste Resource Reuse, School of Ecology and Environment, Inner Mongolia University, Hohhot, 010021, China.

Inner Mongolia Key Laboratory of Environmental Pollution Control & Waste Resource Reuse, School of Ecology and Environment, Inner Mongolia University, Hohhot, 010021, China.

出版信息

Environ Pollut. 2020 Jul;262:114291. doi: 10.1016/j.envpol.2020.114291. Epub 2020 Feb 28.

DOI:10.1016/j.envpol.2020.114291
PMID:32146360
Abstract

Benzotriazole ultraviolet stabilizers (BUVSs) are widely used additives in industrial materials and personal care products that protect products from ultraviolet damage. Due to their high production volume and potential to bioaccumulate, BUVSs are an environmental pollutant of concern. In this study, juvenile zebrafish (Danio rerio) were exposed to 4 BUVSs (UV-234, UV-326, UV-329, and UV-P) at 10 and 100 μg/L for 28 d. BUVSs induced hepatic vacuolization and nuclei pyknosis in the liver following 100 μg/L UV-234 and UV-329 exposure. Transcriptomic analysis in the liver uncovered pathways related to inflammation that were affected by BUVSs. Based upon these data, we measured the expression levels of 9 genes involved in AHR-IL17/IL22 pathway in zebrafish larvae exposed to each BUVSs at one dose of either 10 or 100 μg/L for 6 days in a second set experiment. Transcript levels of interleukins il17a and il22 were decreased, while il6 mRNA was increased with exposure to UV-234, UV-329, and UV-P. No change to targeted transcripts was observed with UV-326 treatments. Moreover, cyp1a1 and ahr2 levels were increased in larvae treated with 100 μg/L UV-329 or UV-P. Consistent with expression data, protein abundance of IL22 was decreased by 29% with exposure to 100 μg/L UV-P. Taken together, these results demonstrate that exposure to different benzotriazole congeners may be associated with immunotoxicity in zebrafish through the AHR-IL17/IL22 pathway, and this may be associated with hepatic damage with prolonged exposures. This study provides new insight into unique pathways perturbed by specific BUVSs congeners.

摘要

苯并三唑紫外线稳定剂(BUVSs)是工业材料和个人护理产品中广泛使用的添加剂,可保护产品免受紫外线伤害。由于其高产量和潜在的生物累积性,BUVSs 是一种令人关注的环境污染物。在这项研究中,幼年斑马鱼(Danio rerio)在 10 和 100μg/L 下暴露于 4 种 BUVSs(UV-234、UV-326、UV-329 和 UV-P)中 28 天。100μg/L UV-234 和 UV-329 暴露后,BUVSs 导致肝脏出现空泡化和核固缩。肝脏的转录组分析揭示了受 BUVSs 影响的与炎症相关的途径。基于这些数据,我们在第二个实验中测量了暴露于每种 BUVSs 10 或 100μg/L 时 6 天,9 种参与 AHR-IL17/IL22 途径的基因在斑马鱼幼虫中的表达水平。白细胞介素 il17a 和 il22 的转录水平降低,而 il6 mRNA 随着 UV-234、UV-329 和 UV-P 的暴露而增加。UV-326 处理未观察到靶向转录物的变化。此外,100μg/L UV-329 或 UV-P 处理的幼虫中 cyp1a1 和 ahr2 水平增加。与表达数据一致,100μg/L UV-P 暴露使 IL22 的蛋白丰度降低了 29%。总之,这些结果表明,不同苯并三唑同系物的暴露可能通过 AHR-IL17/IL22 途径与斑马鱼的免疫毒性有关,并且这可能与长期暴露后的肝损伤有关。这项研究为特定 BUVSs 同系物干扰的独特途径提供了新的见解。

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