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用于研究NLRP3炎性小体生物学的细胞模型与检测方法

Cellular Models and Assays to Study NLRP3 Inflammasome Biology.

作者信息

Zito Giovanni, Buscetta Marco, Cimino Maura, Dino Paola, Bucchieri Fabio, Cipollina Chiara

机构信息

Fondazione Ri.MED, via Bandiera 11, 90133 Palermo, Italy.

Dipartimento di Biomedicina Sperimentale, Neuroscenze e Diagnostica Avanzata (Bi.N.D), University of Palermo, via del Vespro 129, 90127 Palermo, Italy.

出版信息

Int J Mol Sci. 2020 Jun 16;21(12):4294. doi: 10.3390/ijms21124294.

Abstract

The NLRP3 inflammasome is a multi-protein complex that initiates innate immunity responses when exposed to a wide range of stimuli, including pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). Inflammasome activation leads to the release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 and to pyroptotic cell death. Over-activation of NLRP3 inflammasome has been associated with several chronic inflammatory diseases. A deep knowledge of NLRP3 inflammasome biology is required to better exploit its potential as therapeutic target and for the development of new selective drugs. To this purpose, in the past few years, several tools have been developed for the biological characterization of the multimeric inflammasome complex, the identification of the upstream signaling cascade leading to inflammasome activation, and the downstream effects triggered by NLRP3 activation. In this review, we will report cellular models and cellular, biochemical, and biophysical assays that are currently available for studying inflammasome biology. A special focus will be on those models/assays that have been used to identify NLRP3 inhibitors and their mechanism of action.

摘要

NLRP3炎性小体是一种多蛋白复合物,当暴露于多种刺激(包括病原体相关分子模式(PAMPs)和危险相关分子模式(DAMPs))时,会启动先天免疫反应。炎性小体激活导致促炎细胞因子白细胞介素(IL)-1β和IL-18的释放以及细胞焦亡。NLRP3炎性小体的过度激活与几种慢性炎症性疾病有关。为了更好地开发其作为治疗靶点的潜力并开发新的选择性药物,需要深入了解NLRP3炎性小体生物学。为此,在过去几年中,已经开发了几种工具,用于多聚体炎性小体复合物的生物学表征、导致炎性小体激活的上游信号级联的鉴定以及NLRP3激活引发的下游效应。在这篇综述中,我们将报告目前可用于研究炎性小体生物学的细胞模型以及细胞、生化和生物物理分析方法。将特别关注那些用于鉴定NLRP3抑制剂及其作用机制的模型/分析方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f667/7352206/8dbfd58b0821/ijms-21-04294-g001.jpg

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