线粒体的糖酸脱酶复合体控制着炎症性巨细胞中的STAT3-IL-10通路
Dino Gobelli1,2, Pablo Serrano-Lorenzo3,4,5, María J Esteban-Amo1,2
1Department of Cell Biology, Histology and Pharmacology, Faculty of Medicine, University of Valladolid, 47005 Valladolid, Spain.
iScience
|August 14, 2023
概括
线粒体综合体II (糖酸脱酶) 对巨细胞功能至关重要,影响炎症性细胞因子的产生和稳定HIF-1α. 它的缺失会破坏IL-1β和IL-10的释放,影响免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
背景情况:
- 巨细胞的功能是通过代谢调节的,但线粒体电子运输链的作用还没有得到充分研究.
- 糖酸脱酶 (SDH) /复合II (CII) 是ETC的一个关键组成部分.
研究的目的:
- 研究SDH/CII在巨细胞呼吸和效应器反应中的作用.
- 阐明SDH/CII缺乏对炎症性细胞因子产生的影响.
主要方法:
- 使用了缺乏催化子单元Sdha和Sdhb的淘汰性巨细胞.
- 用LPS刺激巨细胞来评估炎症反应.
- 分析了HIF-1α稳定,IL-1β和IL-10产生,Stat3酸化和线粒体活性氧物种 (mitoROS).
主要成果:
- 缺少Sdha和Sdhb会影响巨细胞呼吸和HIF-1α稳定.
- 宏细胞对Sdha/Sdhb的特异性删除抑制了LPS诱导的IL-1β和IL-10的产生.
- SDH/CII 缺乏导致过度的米托ROS积累,并抑制了Stat3 氨酸酸化.
结论:
- SDH/CII对于巨细胞效应因子反应至关重要,包括细胞因子的产生.
- 线粒体功能障碍,以线粒体ROS积累为特征,影响像Stat3酸化这样的炎症信号通路.
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