特里克洛桑及其替代品,特别是赫西丁,调节巨细胞的免疫反应,具有不同的作用模式
Stefanie Raps1, Laura Bahr1, Isabel Karkossa1
1Department of Molecular Toxicology, Helmholtz-Centre for Environmental Research - UFZ, Leipzig, Germany.
The Science of the total environment
|December 30, 2023
概括
特里克洛桑 (TCS) 和其替代的赫西丁 (CHX) 显著改变了免疫细胞的反应. TCS激活炎症通路,而CHX阻止翻译并诱导巨细胞中的压力颗粒,影响免疫调节.
科学领域:
- 免疫学 免疫学 免疫学
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 欧洲监管机构限制了三桑 (TCS) 的使用,需要对替代品进行研究.
- TCS会影响巨细胞中的免疫代谢和炎症酶激活,但对替代品的数据有限.
研究的目的:
- 研究TCS及其替代品对人类巨细胞的分子效应.
- 为了比较TCS和赫西丁 (CHX) 等替代物的作用机制.
主要方法:
- 用LPS刺激的THP-1巨被用TCS或其替代品 (化,化,氧化,CHX,化) 治疗.
- 分析了细胞活力,细胞因子释放 (TNF,IL-1β,IL-6) 和通过LC-MS/MS基蛋白质组的蛋白质表达.
- 通过使用NLRP3抑制剂 (MCC950) 和观察压力颗粒和体形成来评估效应.
主要成果:
- TCS诱导了TNF和IL-1β的释放,表明NLRP3炎症酶激活.
- CHX完全取消了所有研究的细胞因子释放.
- 蛋白质组学揭示了TCS抑制了线粒体电子转移和细胞化,而CHX则导致翻译停止和压力颗粒形成.
- 线粒体和核糖体蛋白质被确定为关键驱动因素;CHX也诱导了受体形成.
结论:
- TCS及其替代品通过不同的分子机制调节巨细胞的免疫反应.
- CHX表现出一种独特的作用模式,阻止翻译并可能降低细胞外基质.
- 这些发现对于免疫调节中TCS替代品的危险评估至关重要.
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