脂肪酸合成通过NLRP3棕化促进炎症酶激活
Stuart Leishman1, Najd M Aljadeed1, Liyunhe Qian1
1Department of Infectious Disease, Imperial College London, London W12 0NN, UK.
Cell reports
|July 18, 2024
概括
脂肪酸合成酶 (FASN) 对于激活NLRP3炎症体至关重要. 抑制FASN或其产物棕化通过阻止NLRP3蛋白转位来阻断炎症酶信号传递.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞的新陈代谢
- 分子生物学分子生物学
背景情况:
- NLRP3炎症酶是关键的免疫传感器,但其通过脂质代谢的调节还不清楚.
- 脂肪酸合成酶 (FASN) 是脂肪酸合成中的一个关键酶.
研究的目的:
- 研究FASN和脂质代谢在NLRP3炎症酶激活中的作用.
- 阐明将FASN活动与炎症体信号传递联系起来的分子机制.
主要方法:
- 在巨细胞和小鼠中FASN的药理和遗传性耗尽.
- 评估炎症酶激活标志物.
- 通过使用化学抑制剂和突变蛋白质,研究棕细胞代谢的作用.
- 使用乙-生物交换试验和免疫光学来追踪蛋白质局部化.
主要成果:
- 在实验室和体内,FASN枯竭显著降低了NLRP3炎症酶激活.
- 抑制FASN活动或细胞棕化损害了炎症体信号传递.
- NLRP3炎症酶激活涉及Cys898的棕化,促进其转移到跨戈尔吉网络.
- 一种NLRP3的Cys898突变体显示了棕化减少和转位和激活受损.
结论:
- 脂肪酸合成酶 (FASN) 在许可NLRP3炎症酶组合和激活方面发挥着关键作用.
- 由FASN活动调解的NLRP3的棕化对于其适当的局部化和随后的炎症细胞组合至关重要.
- 这项研究揭示了脂质代谢与通过NLRP3炎症体的先天性免疫感知之间的直接联系.
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