The Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Antrim, UK.
J Leukoc Biol. 2020 Sep;108(3):937-952. doi: 10.1002/JLB.3MR0720-513R. Epub 2020 Aug 3.
The NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome is an immunological sensor that detects a wide range of microbial- and host-derived signals. Inflammasome activation results in the release of the potent pro-inflammatory cytokines IL-1β and IL-18 and triggers a form of inflammatory cell death known as pyroptosis. Excessive NLRP3 activity is associated with the pathogenesis of a wide range of inflammatory diseases, thus NLRP3 activation mechanisms are an area of intensive research. NLRP3 inflammasome activation is a tightly regulated process that requires both priming and activation signals. In particular, recent research has highlighted the highly complex nature of the priming step, which involves transcriptional and posttranslational mechanisms, and numerous protein binding partners. This review will describe the current understanding of NLRP3 priming and will discuss the potential opportunities for targeting this process therapeutically to treat NLRP3-associated diseases.
NLRP3（NOD、LRR 和 pyrin 结构域蛋白 3）炎性小体是一种免疫传感器，可检测广泛的微生物和宿主来源的信号。炎性小体的激活导致强效促炎细胞因子 IL-1β 和 IL-18 的释放，并引发一种称为细胞焦亡的炎症细胞死亡形式。NLRP3 活性过度与多种炎症性疾病的发病机制有关，因此 NLRP3 激活机制是一个研究热点。NLRP3 炎性小体的激活是一个严格调控的过程，需要激活信号和初始信号。特别是，最近的研究强调了初始步骤的高度复杂性质，该步骤涉及转录和翻译后机制以及许多蛋白质结合伙伴。这篇综述将描述目前对 NLRP3 初始信号的理解，并讨论靶向该过程治疗 NLRP3 相关疾病的潜在机会。
