Research progress of NLRP3 inflammasome in lupus nephritis

Lupus nephritis (LN) is one of the most severe clinical complications of systemic lupus erythematosus (SLE), It significantly impairs the quality of life and prognosis of SLE patients, and is associated with a higher incidence of chronic kidney disease (CKD) and mortality in patients with CKD. The NLRP3 inflammasome is a multi-protein complex belonging to the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family. It consists of the following proteins: ASC, NLRP3, and pro-caspase-1. The inflammasome can be activated via three distinct pathways: the classical pathway, the non-classical pathway, and the alternative pathway. The process of activation has been demonstrated to initiate the release of pro-inflammatory cytokines, thus inducing tissue and cellular damage. It has been determined that this process plays a pivotal role in the pathogenesis of numerous autoimmune diseases, including LN. In LN, the NLRP3 inflammasome exerts pathological effects on various renal cells, particularly podocytes and renal tubular cells. Enhanced fluorescence localization and elevated protein expression of the NLRP3 inflammasome (and its core components) can be detected in these cells. It has been established that multiple upstream regulatory factors, including members of the guanylate-binding protein (GBP) family (GBP3, GBP5), CD36, PIM1, IRF2, and S1P, have the capacity to activate the NLRP3 inflammasome and its associated components. This process serves to initiate inflammatory responses and accelerate LN progression. Furthermore, a number of studies have successfully alleviated and treated LN by inhibiting the activation of the NLRP3 inflammasome. This inhibition can be accomplished through two main approaches: the following methods have been employed to increase the expression of endogenous factors such as FGF21 and SIRT1; increasing the expression of endogenous factors exogenously using agents including phytochemicals (e.g.; honokiol, epigallocatechin gallate, procyanidin B2, icaritin, luteolin, the active metabolite M1 of ginsenoside Rg1, ursolic acid, total notoginsenoside saponins, and citral); the NLRP3 inhibitor MCC950, the nuclear factor-κB (NF-κB) inhibitor Bay11-7082; melatonin; xenon; and notoginseng injection. All these strategies improve the progression and prognosis of LN by suppressing the activation of the NLRP3 inflammasome. This article systematically summarizes the composition and activation mechanism of the NLRP3 inflammasome, as well as its activation factors in LN. In addition, it explores treatment strategies for LN targeting the NLRP3 inflammasome, particularly emphasizing the potential therapeutic effects of phytochemicals. This article provides new ideas for the development of LN-related drugs and treatment plans.