mtDNA通过16HBE细胞的cGAS-STING通路放大酸诱导的炎症反应
Xiaodong Liu1,2, Tianyi Jiang1,2, Huiyun Jin1,2
1Department of Preventive Medicine, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China.
Journal of applied toxicology : JAT
|May 22, 2024
概括
硫酸 (BeSO4) 通过破坏线粒体和释放线粒体DNA (mtDNA) 来引发炎症. 这种释放的mtDNA激活cGAS-STING通路,促进肺细胞的炎症反应.
科学领域:
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 已知硫酸 (BeSO4) 诱导炎症,但潜在的机制尚不清楚.
- 线粒体DNA (mtDNA) 越来越被认为是启动炎症过程的关键因素.
- 释放的mtDNA可以与cGAS等细胞受体相互作用,激活驱动炎症的信号通路.
研究的目的:
- 调查线粒体DNA (mtDNA) 在16HBE细胞中硫酸 (BeSO4) 诱导的炎症中的作用.
- 阐明涉及BeSO4诱导的炎症反应的特定分子途径.
主要方法:
- 已确立的BeSO4诱导的16HBE细胞炎症和乙基 (EB) 诱导的p016HBE细胞模型.
- 评估了mtDNA含量,氧化应激标志物,线粒体膜潜力和cGAS-STING通路表达.
- 测量了与炎症相关的因素水平,包括IL-10,TNF-α和IFN-β.
主要成果:
- BeSO4暴露导致氧化应激,线粒体膜潜能降低,mtDNA释放到16HBE细胞的细胞质中.
- BeSO4激活了cGAS-STING通路,导致炎症.
- mtDNA删除抑制了cGAS-STING通路,并降低了IL-10,TNF-α和IFN-β的表达.
结论:
- 这项研究揭示了一种新的机制,即BeSO4通过mtDNA释放和随后的cGAS-STING通路激活来诱导16HBE细胞的炎症.
- 这些发现有助于我们更好地理解化合物在分子水平上的毒性.
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