Ma Wenxiang, Wang Yilei, Liu Jinfeng
Department of Pharmacy, Taicang TCM Hospital, Affiliated to Nanjing University of Chinese Medicine, Taicang, Jiangsu, People's Republic of China.
School of Medicine, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
J Inflamm Res. 2025 Jun 24;18:8277-8294. doi: 10.2147/JIR.S532908. eCollection 2025.
The NOD-like receptor protein 3 (NLRP3) inflammasome, a cytosolic multi-protein complex, detects danger signals released by injured cells and pathogens. It plays a critical role in the pathogenesis of various acute and chronic liver diseases. NLRP3 activation triggers caspase-1-mediated processing and secretion of pro-inflammatory cytokines interleukin (IL)-1β and IL-18. Unlike other inflammatory pathways, NLRP3 activation requires two signals, ensuring a tight control over inflammation. Caspase-1 activation further amplifies the response by cleaving IL-1β, a potent pro-inflammatory mediator. Extensive research suggests the NLRP3 inflammasome contributes significantly to hepatocyte injury, immune cell activation, and the perpetuation of inflammatory responses in various human and experimental liver disease models. This review comprehensively examines NLRP3 inflammasome activation and its functional consequences in the context of liver injury and disease progression, including conditions such as alcoholic liver disease (ALD), metabolic dysfunction-associated fatty liver disease (MAFLD), viral hepatitis, hepatic fibrosis, and drug-induced liver injury (DILI). We specifically highlight emerging therapeutic strategies targeting NLRP3 inflammasome that show translational promise in attenuating liver inflammation and fibrosis. This review provides a theoretical framework and reference for the development of novel therapeutics targeting the NLRP3 inflammasome in liver injury and chronic liver diseases.
NOD样受体蛋白3（NLRP3）炎性小体是一种胞质多蛋白复合物，可检测受损细胞和病原体释放的危险信号。它在各种急慢性肝病的发病机制中起关键作用。NLRP3激活触发胱天蛋白酶-1介导的促炎细胞因子白细胞介素（IL）-1β和IL-18的加工和分泌。与其他炎症途径不同，NLRP3激活需要两个信号，以确保对炎症的严格控制。胱天蛋白酶-1激活通过切割强效促炎介质IL-1β进一步放大反应。广泛的研究表明，NLRP3炎性小体在各种人类和实验性肝病模型中对肝细胞损伤、免疫细胞激活以及炎症反应的持续存在有显著贡献。本综述全面研究了在肝损伤和疾病进展背景下NLRP3炎性小体的激活及其功能后果，包括酒精性肝病（ALD）、代谢功能障碍相关脂肪性肝病（MAFLD）、病毒性肝炎、肝纤维化和药物性肝损伤（DILI）等情况。我们特别强调了针对NLRP3炎性小体的新兴治疗策略，这些策略在减轻肝脏炎症和纤维化方面显示出转化前景。本综述为开发针对肝损伤和慢性肝病中NLRP3炎性小体的新型疗法提供了理论框架和参考。
