三3A通过NFκB-氧化通路参与了对内毒素耐受性和真菌杀菌活性的调节
Yongwei Qin1,2, Jinliang Chen3, Kuang Xu2
1Department of Clinical Laboratory, The Sixth People's Hospital of Nantong, Nantong, Jiangsu, China.
Immunity, inflammation and disease
|July 28, 2023
概括
三3A调节巨细胞中的内毒素耐受性,影响败血症. 降低miR-191的调节影响Triad3A和TRAF3,影响TLR4-NF-κB-NO通路,并在败血症中杀死菌根菌.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 败血症表现出一种内毒素耐受性表型,可能导致持续感染期间免疫细胞耗尽.
- 众所周知,Triad3A是一种E3泛素酶,可以负面调节Toll-like受体4 (TLR4) 激活.
- Triad3A对内毒素耐受性和杀菌能力的具体作用尚不清楚.
研究的目的:
- 调查Triad3A在调节内毒素耐受性的作用及其对杀菌能力的影响.
- 在内毒素耐受性的背景下,探索miR-191,Triad3A和TRAF3之间的关系.
- 阐明Triad3A在败血症中的功能背后的分子机制.
主要方法:
- 用脂聚糖 (LPS) 刺激巨细胞系以诱导内毒素耐受性.
- 对基因和蛋白质表达的分析,包括miR-191,Triad3A,TRAF3,TLR4,p-P65,TNF-α,IL-1β和iNOS.
- 基因功能丧失研究和对Triad3A对TLR4-NF-κB-NO通路和杀死菌根菌的作用的调查.
主要成果:
- 发现Triad3A参与调节巨细胞内毒素耐受性表型.
- 在耐受内毒素巨细胞中,miR-191的表达下调,直接与Triad3A和TRAF3.3结合.
- 敲除 Triad3A 逆转了 TNF-α 和 IL-1β 的下降,而 TLR4-NF-κB-NO 途径与 Triad3A 介导的细胞内菌根杀死有关.
结论:
- 在毒症期间,Triad3A在巨细胞中诱导耐受性表型方面发挥着至关重要的作用.
- 了解 Triad3A 的机制,可以了解败血症休克的病原性,特别是 Mycobacterium 结核病感染.
- 三3A成为严重的败血结核病的潜在治疗点.
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