NLRP3 炎性小体：激活与调控。
The NLRP3 inflammasome: activation and regulation.
机构信息
Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
出版信息
Trends Biochem Sci. 2023 Apr;48(4):331-344. doi: 10.1016/j.tibs.2022.10.002. Epub 2022 Nov 4.
Abstract
The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is a cytoplasmic supramolecular complex that is activated in response to cellular perturbations triggered by infection and sterile injury. Assembly of the NLRP3 inflammasome leads to activation of caspase-1, which induces the maturation and release of interleukin-1β (IL-1β) and IL-18, as well as cleavage of gasdermin D (GSDMD), which promotes a lytic form of cell death. Production of IL-1β via NLRP3 can contribute to the pathogenesis of inflammatory disease, whereas aberrant IL-1β secretion through inherited NLRP3 mutations causes autoinflammatory disorders. In this review, we discuss recent developments in the structure of the NLRP3 inflammasome, and the cellular processes and signaling events controlling its assembly and activation.
摘要
NOD、LRR 和 pyrin 结构域包含蛋白 3（NLRP3）炎症小体是一种细胞质超分子复合物，可响应感染和非感染性损伤引发的细胞扰动而被激活。NLRP3 炎症小体的组装导致半胱天冬酶-1 的激活，诱导白细胞介素-1β（IL-1β）和白细胞介素-18 的成熟和释放，以及天冬氨酸特异性半胱氨酸蛋白酶-3（caspase-3）的切割，促进细胞裂解死亡的形式。通过 NLRP3 产生的白细胞介素-1β可导致炎症性疾病的发病机制，而通过遗传性 NLRP3 突变导致的异常白细胞介素-1β分泌会引起自身炎症性疾病。在这篇综述中，我们讨论了 NLRP3 炎症小体的结构以及控制其组装和激活的细胞过程和信号事件的最新进展。
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