Department of Genetics, Trinity College Dublin, Dublin, Ireland.
Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland ; National Children's Research Centre, Our Lady's Children's Hospital Crumlin, Dublin, Ireland.
J Inflamm Res. 2015 Jan 16;8:15-27. doi: 10.2147/JIR.S51250. eCollection 2015.
The inflammasome is a molecular platform formed by activation of an innate immune pattern recognition receptor seed, such as NLRP3. Once activated, NLRP3 recruits the adapter ASC (apoptosis-related speck-like protein containing a caspase recruitment domain), which in turn recruits procaspase-1. Procaspase-1 autocatalyzes its cleavage and activation, resulting in maturation of the precursor forms of interleukin (IL)-1β and IL-18 into active proinflammatory cytokines and initiation of pyroptotic cell death. The NLRP3 inflammasome has been implicated in the pathogenesis of a wide variety of diseases, including genetically inherited autoinflammatory conditions as well as chronic diseases in which NLRP3 is abnormally activated. The NLRP3 inflammasome has been linked to diseases such as Alzheimer's disease, atherosclerosis, metabolic syndrome, and age-related macular degeneration. In this review, we describe the NLRP3 inflammasome complex and its activation in disease, and detail the current therapies that modulate either the NLRP3 inflammasome complex itself or the two cytokines it is responsible for activating, ie, IL-1β and IL-18.
炎症小体是一种由先天免疫模式识别受体（如 NLRP3）激活而形成的分子平台。一旦被激活，NLRP3 会招募衔接蛋白 ASC（含半胱氨酸蛋白酶募集结构域的凋亡相关斑点样蛋白），后者反过来又会招募前体胱冬肽酶-1。前体胱冬肽酶-1 自我催化其切割和激活，导致白细胞介素 (IL)-1β 和 IL-18 的前体形式成熟为活性促炎细胞因子，并启动细胞焦亡。NLRP3 炎症小体与多种疾病的发病机制有关，包括遗传性自身炎症性疾病以及 NLRP3 异常激活的慢性疾病。NLRP3 炎症小体与阿尔茨海默病、动脉粥样硬化、代谢综合征和年龄相关性黄斑变性等疾病有关。在这篇综述中，我们描述了 NLRP3 炎症小体复合物及其在疾病中的激活，并详细介绍了目前调节 NLRP3 炎症小体复合物本身或其负责激活的两种细胞因子（即 IL-1β 和 IL-18）的治疗方法。
