膜结合的INTERLEUKIN-1α在动脉生成过程中调解白细胞粘附
Christina Maeder1, Thimoteus Speer2,3, Angela Wirth4,5
1Klinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, Leipzig University, Leipzig, Germany.
Frontiers in immunology
|September 13, 2023
概括
细胞表面的互白素-1α (IL-1α) 驱动动动脉硬化,独立于NLRP3炎症酶. IL-1α转移到髓状细胞表面促进白细胞粘附和斑块发育,突出了一个新的治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
- 炎症研究 炎症研究
背景情况:
- 互白素-1 (IL-1) 家族和NLRP3炎症酶与动脉样硬化有关.
- 将IL-1α,IL-1β和NLRP3与动脉样硬化相关联的机制需要进一步阐明.
- IL-1α具有独立于NLRP3炎症酶的促炎作用.
研究的目的:
- 研究IL-1α,IL-1β和NLRP3在动脉样硬化病原发生中的不同作用.
- 描述IL-1α有助于动脉样硬化发展的机制.
主要方法:
- 使用PCSK9-AAV8突变病毒和高脂肪饮食的非遗传模型用于野生类型和淘汰赛小鼠 (Il1a-/-,Nlrp3-/-,Il1b-/-).
- 分析了动脉样硬化斑块区域,脂质积累和血清细胞因子水平.
- 细胞机制涉及IL-1α转位,基化和蛋白质-蛋白质相互作用在髓状细胞和内皮细胞中被检查.
主要成果:
- 与对照组相比,PCSK9-Il1a-/-小鼠的动脉样硬化斑块面积和脂质积累显著减少.
- 在PCSK9-Nlrp3-/-或PCSK9-Il1b-/-小鼠中没有观察到动脉样硬化的显著差异.
- 通过myristoylation调节的IL-1α转移到髓状细胞的细胞表面 (csIL-1α) 被观察到并与高胆固醇血症相关.
- 在内皮细胞上,cSIL-1α与IL1R1的相互作用促进了VCAM1的表达和单细胞粘附,而这种粘附被中和抗体阻断.
结论:
- 循环白细胞表面的IL-1α对动脉样硬化发展至关重要.
- 在Il1a-/-小鼠中,对动脉样硬化的保护独立于循环中的细胞因子和NLRP3炎症酶活性.
- 在髓状细胞中依赖于密斯托化的IL-1α细胞表面转位有助于白细胞粘附和动脉样硬化进展.
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