NLRP3炎症小体的活化机制及其抑制剂在关节炎症性疾病中的研究进展

Research Progress in Activation Mechanism of Inflammasome NLRP3 and Its Inhibitors in Joint Inflammatory Diseases

核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)是炎症反应的核心,其异常活化后可通过参与调节胱天蛋白酶1(caspase-1)的活化,促进白细胞介素(IL)-1β前体和IL-18前体的成熟和分泌,还可调节caspase-1依赖的细胞凋亡,诱导细胞在炎症及应激条件下死亡,与多种疾病密切相关。NLRP3在关节炎症性疾病中表达异常,部分NLRP3炎症小体抑制剂对关节炎症性疾病的治疗已进入Ⅱ~Ⅲ期临床试验阶段。深入研究NLRP3炎症小体的活化机制及其抑制剂在关节炎症性疾病中的作用,可为关节炎症性疾病的治疗提供新思路。

Nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)is the core of inflammatory response.Abnormal activation of NLRP3 can promote the maturation and secretion of cytokines pro-interleukin(IL)-1βand pro-IL-18 by participating in the regulation of caspase-1 activation.It can also regulate caspase-1-dependent apoptosis and induce cell death under inflammatory and stress conditions,which is closely related to a variety of diseases.NLRP3 is abnormally expressed in joint inflammatory diseases,and some NLRP3 inflammasome inhibitors have entered stageⅡ-Ⅲclinical trials for the treatment of joint inflammation.Further study on the activation mechanism of NLRP3 inflammasome and the role of its inhibitors in joint inflammatory diseases can provide new ideas for the treatment of joint inflammatory diseases.