Loop Between NLRP3 Inflammasome and Reactive Oxygen Species
Loop Between NLRP3 Inflammasome and Reactive Oxygen Species
复制标题
NLRP3炎性体和活性氧之间的环路
DOI：
10.1089/ars.2020.8257
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发表时间：
2022-01-17
影响因子：
6.6
通讯作者：
Takahashi, Masafumi
中科院分区：
文献类型：
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作者：
Dominic, Abishai;Le, Nhat-Tu;Takahashi, Masafumi
意义：炎症小体是介导先天免疫途径的胞质多蛋白复合物。炎性体激活炎性半胱天冬酶并调节炎性细胞因子白细胞介素 (IL)-1β 和 IL-18 以及炎性细胞死亡（焦亡）。在已知的炎症小体中，NLRP3（含有 3 个吡啶结构域的 NLR 家族）炎症小体是独特的，并且得到了充分研究，因为它能够感知广泛的刺激，并且与微生物和无菌炎症疾病的发病机制有关。 最新进展：活性氧 (ROS)，特别是来自线粒体的活性氧，是 NLRP3 的关键介质之一 炎症小体激活。此外，NLRP3 炎症小体驱动的炎症会招募巨噬细胞和中性粒细胞等炎症细胞，进而导致 ROS 产生，表明 ROS 和 NLRP3 炎症小体之间存在反馈循环。 关键问题：ROS 如何影响 NLRP3 炎症小体激活的精确机制仍需解决。本综述将总结当前关于 NLRP3 炎症小体激活分子机制的知识，特别强调 ROS 和炎症小体激活之间反馈环路的复杂平衡。未来方向：了解这种关系是循环而不是传统理解的线性机制，将能够在不同的病理环境下微调炎症小体激活。
Significance: Inflammasomes are cytosolic multiprotein complexes that mediate innate immune pathways. Inflammasomes activate inflammatory caspases and regulate inflammatory cytokines interleukin (IL)-1 beta and IL-18 as well as inflammatory cell death (pyroptosis). Among known inflammasomes, NLRP3 (NLR family pyrin domain containing 3) inflammasome is unique and well studied owing to the fact that it senses a broad range of stimuli and is implicated in the pathogenesis of both microbial and sterile inflammatory diseases.Recent Advances: Reactive oxygen species (ROS), especially derived from the mitochondria, are one of the critical mediators of NLRP3 inflammasome activation. Furthermore, NLRP3 inflammasome-driven inflammation recruits inflammatory cells, including macrophages and neutrophils, which in turn cause ROS production, suggesting a feedback loop between ROS and NLRP3 inflammasome.Critical Issues: The precise mechanism of how ROS affects NLRP3 inflammasome activation still need to be addressed. This review will summarize the current knowledge on the molecular mechanisms underlying the activation of NLRP3 inflammasome with particular emphasis on the intricate balance of feedback loop between ROS and inflammasome activation.Future Directions: Understanding that this relationship is loop rather than traditionally understood linear mechanism will enable to fine-tune inflammasome activation under varied pathological settings.