Bakhshi Saba, Shamsi Saeedeh
Department of Pharmacology, School of the Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
Department of Pharmacology, School of the Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
Int Immunopharmacol. 2022 May;106:108595. doi: 10.1016/j.intimp.2022.108595. Epub 2022 Feb 3.
Evidence suggests that various innate immune system components are involved in pathological inflammatory conditions. Among these components, the NLR family pyrin domain containing 3 (NLRP3) as an inflammasome can participate in destructive inflammatory responses by inducing the production of the active form of inflammatory cytokines. The NLRP3 could be involved in the pathogenesis of several inflammatory and autoimmune diseases such as type 2 diabetes mellitus, multiple sclerosis (MS), atherosclerosis, Alzheimer's disease (AD), cryopyrin-associated periodic syndrome (CAPS), and infectious diseases. Therefore, the inhibition of NLRP3 can be a useful treatment option for inflammatory diseases. In this regard, MCC950, as a small molecule, is capable of inhibiting NLRP3 and, following inhibition of NLRP3, production of interleukin-1β (IL-1β) and IL-18 as pro-inflammatory cytokines reduced. Interestingly, the MCC950 can inhibit NLRP3 but no other inflammasomes such as NLRP1 and NLR family CARD domain containing 4 (NLRC4). This review summarized the structure and mechanism of action of MCC950 in the control of NLRP3-dependent inflammation and the role of MCC950 in the treatment of NLRP3-mediated inflammatory diseases based on the latest studies.
有证据表明,各种先天性免疫系统成分参与了病理性炎症状态。在这些成分中,含吡啉结构域的NLR家族成员3(NLRP3)作为一种炎性小体,可通过诱导炎性细胞因子活性形式的产生参与破坏性炎症反应。NLRP3可能参与多种炎症和自身免疫性疾病的发病机制,如2型糖尿病、多发性硬化症(MS)、动脉粥样硬化、阿尔茨海默病(AD)、冷吡啉相关周期性综合征(CAPS)以及感染性疾病。因此,抑制NLRP3可能是治疗炎症性疾病的一种有效选择。在这方面,MCC950作为一种小分子,能够抑制NLRP3,并且在抑制NLRP3后,促炎细胞因子白细胞介素-1β(IL-1β)和IL-18的产生减少。有趣的是,MCC950可以抑制NLRP3,但不能抑制其他炎性小体,如NLRP1和含CARD结构域的NLR家族成员4(NLRC4)。本综述基于最新研究总结了MCC950在控制NLRP3依赖性炎症中的结构和作用机制,以及MCC950在治疗NLRP3介导的炎症性疾病中的作用。