和多醇基物质通过炎症性细胞因子-IL-17/Th17信号轴触发自身免疫性疾病
Qi Cheng1, Yifan Xie1, Yingying Hou2
1Department of Rheumatology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China.
Chemico-biological interactions
|November 20, 2025
概括
暴露在和多基物质 (PFAS) 中可以破坏免疫系统,并通过影响关键炎症通路引发自身免疫疾病 (ADs). 某些PFAS替代品可能会带来更大的健康风险,需要重新评估.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 免疫学 免疫学 免疫学
背景情况:
- 和多基基物质 (PFAS) 是广泛使用的化学物质,与各种健康问题有关.
- 免疫失调和自身免疫性疾病 (ADS) 是一个重大的公共卫生挑战.
- 连接PFAS暴露与AD病原体的精确分子机制仍然不完全理解.
研究的目的:
- 阐明PFAS暴露导致免疫失调和自身免疫性疾病的分子机制.
- 确定共享的分子标和途径,将PFAS暴露与五种特定的AD联系起来:类风湿性关节炎,全身性红斑狼,Sjögren综合征,结性脊髓炎和血管炎.
- 为了比较不同PFAS的结合性亲缘关系,包括替代品,以确定潜在的风险.
主要方法:
- 综合网络毒理学和生物信息学方法使用数据库,如STITCH,瑞士目标预测,CTD,基因卡和OMIM.
- 功能丰富分析 (DAVID) 和蛋白质与蛋白质相互作用网络的构建 (STRING,Cytoscape).
- 分子对接模拟 (CB-Dock2) 和基因表达数据分析 (GEO数据库).
主要成果:
- 确定了共同的分子标和途径,涉及到PFAS暴露和AD病原体.
- 证实了几种PFAS对核心标的强有力的结合,包括IL1B,TNF和IL6.
- 揭示了一种常见的机制,涉及PFAS诱导的炎症细胞因子轴和IL-17/Th17信号通路的破坏.
- 6:2 Cl-PFESA与PFOS相比,对核心目标具有更高的结合亲和力,这表明潜在的风险更大.
结论:
- 暴露于PFAS可以通过破坏关键的炎症信号通路引发自身免疫性疾病.
- 提供了对PFAS诱导免疫毒性的分子机制及其与ADS的联系的新见解.
- 这些发现强调了需要重新评估某些PFAS替代品,因为潜在的更高的健康风险.
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