State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Clin Exp Allergy. 2018 Sep;48(9):1080-1091. doi: 10.1111/cea.13190. Epub 2018 Jul 3.
Allergic diseases, such as asthma, rhinitis, dermatitis, conjunctivitis, and anaphylaxis, have recently become a global public health concern. According to previous studies, the NLRP3 inflammasome is a multi-protein complex known to be associated with many inflammatory conditions. In response to allergens or allergen/damage-associated molecular signals, NLRP3 changes its conformation to allow the assembly of the NLRP3 inflammasome complex and activates caspase-1, which is an evolutionarily conserved enzyme that proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines IL-1β and IL-18. Subsequently, active caspase-1 cleaves pro-IL-1 and pro-IL-18. Recently, accumulating human and mouse experimental evidence has demonstrated that the NLRP3 inflammasome, IL-1β, and IL-18 are critically involved in the development of allergic diseases. Furthermore, the application of specific NLRP3 inflammasome inhibitors has been demonstrated in animal models. Therefore, these inhibitors may represent potential therapeutic methods for the management of clinical allergic disorders. This review summarizes findings related to the NLRP3 inflammasome and its related factors and concludes that specific NLRP3 inflammasome inhibitors may be potential therapeutic agents for allergic diseases.
过敏性疾病,如哮喘、鼻炎、皮炎、结膜炎和过敏反应,已成为全球公共卫生关注的焦点。根据之前的研究,NLRP3 炎性小体是一种与许多炎症状态相关的多蛋白复合物。NLRP3 在响应过敏原或过敏原/损伤相关的分子信号时,改变其构象以允许 NLRP3 炎性小体复合物的组装,并激活半胱天冬酶-1,这是一种进化上保守的酶,可蛋白水解切割其他蛋白质,如炎性细胞因子 IL-1β 和 IL-18 的前体。随后,活性半胱天冬酶-1切割 pro-IL-1 和 pro-IL-18。最近,越来越多的人类和小鼠实验证据表明,NLRP3 炎性小体、IL-1β 和 IL-18 都与过敏性疾病的发展密切相关。此外,在动物模型中已经证明了特定的 NLRP3 炎性小体抑制剂的应用。因此,这些抑制剂可能代表管理临床过敏性疾病的潜在治疗方法。这篇综述总结了与 NLRP3 炎性小体及其相关因素有关的发现,并得出结论,特定的 NLRP3 炎性小体抑制剂可能是治疗过敏性疾病的潜在治疗剂。