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人类NLRP1炎症酶的流驱动激活的机制基础

Pritisha Rozario¹, Miriam Pinilla², Leana Gorse²

¹Lee Kong Chian School of Medicine, Nanyang Technological University, 308232, Singapore.

Proceedings of the National Academy of Sciences of the United States of America

|January 4, 2024

概括

尼格瑞通过耗尽离子来激活NLRP1炎症体,抑制核糖体延长并触发核糖毒应激反应 (RSR). 这种机制不同于NLRP3炎症酶激活,强调了离子流和天生的免疫之间的联系.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
细胞生物学细胞生物学

背景情况:

尼格瑞是一种广泛使用的工具化合物,用于研究NLRP3炎症酶.
新出现的证据表明,尼日里辛还可以激活人类角质细胞中的NLRP1炎症体.
尼日里辛诱导的NLRP1激活的确切机制尚不清楚.

研究的目的:

阐明尼日里辛驱动的NLRP1炎症酶激活的机制基础.
调查离子耗尽和 рибо毒性应激反应 (RSR) 在NLRP1激活中的作用.
要区分NLRP1的激活机制与NLRP3的激活机制.

主要方法:

利用了多种非血造细胞类型.
评估了尼日里辛对核糖体延长和细胞酸水平的影响.
研究了ZAKα,p38和JNK激酶的激活.
检查了NLRP1链接域酸化.
评估了细胞外补充剂,ZAKα敲击和激酶抑制剂对尼日里辛诱导的热的作用.
选了各种离子体以确定ZAKα驱动的RSR激活的要求.

主要成果:

尼格瑞通过耗尽细胞酸离子来抑制核糖体延长.
这种耗耗激活ZAKα激酶,导致p38和JNK激活和NLRP1链接域过酸化.
尼日里诱导的角质细胞中的热可以通过恢复水平或抑制ZAKα/p38.
离子运动的电子中立性对于ZAKα驱动的RSR至关重要.
对于ZAKα-NLRP1激活,需要比NLRP3激活更大的耗.

结论:

尼格瑞通过ZAKα介导的核毒性应激反应激活NLRP1炎症酶,而这种反应是由耗尽引发的.
这项研究揭示了在非造血细胞中NLRP1炎症酶激活的新机制.
建立了一种意想不到的链接 ribotoxic 应激反应,离子流和先天免疫.

关键词:

在NLRP1中,NLRP1是NLRP1中的一个.一些炎症一些炎症这是先天免疫力.尼格里西尼尼尼格里西尼尼尼的外流是因为.

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