Department of Rheumatology and Immunology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Expert Opin Drug Discov. 2021 Apr;16(4):429-446. doi: 10.1080/17460441.2021.1844179. Epub 2020 Dec 21.
: Inflammatory reactions, including those mediated by the NLRP3 inflammasome, maintain the body's homeostasis by removing pathogens, repairing damaged tissues, and adapting to stressed environments. However, uncontrolled activation of the NLRP3 inflammasome tends to cause various diseases using different mechanisms. Recently, many inhibitors of the NLRP3 inflammasome have been reported and many are being developed. In order to assess their efficacy, specificity, and mechanism of action, the screening process of inhibitors requires various types of cell and animal models of NLRP3-associated diseases.: In the following review, the authors give an overview of the cell and animal models that have been used during the research and development of various inhibitors of the NLRP3 inflammasome.: There are many NLRP3 inflammasome inhibitors, but most of the inhibitors have poor specificity and often influence other inflammatory pathways. The potential risk for cross-reaction is high; therefore, the development of highly specific inhibitors is essential. The selection of appropriate cell and animal models, and combined use of different models for the evaluation of these inhibitors can help to clarify the target specificity and therapeutic effects, which is beneficial for the development and application of drugs targeting the NLRP3 inflammasome.
炎症反应，包括由 NLRP3 炎性小体介导的反应，通过清除病原体、修复受损组织和适应应激环境来维持身体的内稳态。然而，NLRP3 炎性小体的失控激活往往会通过不同的机制导致各种疾病。最近，已经报道了许多 NLRP3 炎性小体的抑制剂，并且正在开发许多抑制剂。为了评估它们的疗效、特异性和作用机制，抑制剂的筛选过程需要各种类型的 NLRP3 相关疾病的细胞和动物模型。在以下综述中，作者概述了在研究和开发各种 NLRP3 炎性小体抑制剂过程中使用的细胞和动物模型。 NLRP3 炎性小体抑制剂有很多，但大多数抑制剂特异性差，往往影响其他炎症途径。交叉反应的潜在风险很高；因此，开发高特异性抑制剂至关重要。选择适当的细胞和动物模型，并结合使用不同的模型来评估这些抑制剂，可以帮助阐明靶特异性和治疗效果，这有利于 NLRP3 炎性小体靶向药物的开发和应用。
