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长期暴露于环境水平的菲引起小鼠肾脏的适应性免疫反应和纤维化。

Long-term exposure to environmental level of phenanthrene causes adaptive immune response and fibrosis in mouse kidneys.

机构信息

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, The 5th Hospital of Xiamen, Xiang'an Branch of the First Affiliated Hospital, Xiamen University, Xiamen, Fujian, 361102, China.

Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai, 200025, China.

出版信息

Environ Pollut. 2021 Aug 15;283:117028. doi: 10.1016/j.envpol.2021.117028. Epub 2021 Mar 31.

DOI:10.1016/j.envpol.2021.117028
PMID:33892371
Abstract

As ubiquitous, persistent organic pollutants, polycyclic aromatic hydrocarbons (PAHs) have adverse impacts on human health. Phenanthrene (Phe) is one of the most abundant PAHs in the environment. However, the long-term effects of exposure to environmental level of Phe on the kidneys and the potential mechanisms are unclear. T helper (Th) cells, a subtype of CD4 T cells that play a central role in the renal immune microenvironment. In this study, male mice were chronically exposed to 5, 50, and 500 ng/kg bw Phe every other day for total 210 days. Those results indicated that environmental Phe exposure caused kidney hypertrophy, injury and fibrosis in the mice. Chronic, long-term environmental level of Phe exposure did not significantly alter the innate immune response but induced adaptive immune response changes (Th1/Th2 related cytokines release), causing a type 1 immune response in the 5 ng/kg bw Phe group and a type 2 immune response in the high dose groups (50 and 500 ng/kg bw). This study provides novel insights into the roles of adaptive immune response in long-term PAH exposure-induced chronic kidney injury and fibrosis, which is beneficial for further understanding the potential health hazards of PAHs and providing new avenues for immune intervention strategies to alleviate PAHs toxicity.

摘要

多环芳烃(PAHs)作为普遍存在且持久的有机污染物,对人类健康具有不良影响。菲(Phe)是环境中最丰富的 PAHs 之一。然而,暴露于环境水平的 Phe 对肾脏的长期影响及其潜在机制尚不清楚。辅助性 T 细胞(Th)是 CD4 T 细胞的一个亚型,在肾脏免疫微环境中发挥核心作用。在这项研究中,雄性小鼠每隔一天接受 5、50 和 500ng/kg bw 的 Phe 慢性暴露,总共 210 天。结果表明,环境 Phe 暴露导致小鼠肾脏肥大、损伤和纤维化。慢性、长期的环境水平的 Phe 暴露并未显著改变固有免疫反应,但诱导适应性免疫反应变化(Th1/Th2 相关细胞因子释放),导致 5ng/kg bw Phe 组发生 1 型免疫反应,高剂量组(50 和 500ng/kg bw)发生 2 型免疫反应。本研究为适应性免疫反应在长期 PAH 暴露引起的慢性肾脏损伤和纤维化中的作用提供了新的见解,有助于进一步了解 PAHs 的潜在健康危害,并为免疫干预策略提供新途径以减轻 PAHs 的毒性。

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