An update on cell intrinsic negative regulators of the NLRP3 inflammasome

Abstract

Inflammasomes are multimeric protein complexes that promote inflammation (through specific cleavage and production of bioactive IL-1β and IL-18) and pyroptotic cell death. The central role of inflammasomes in combating infection and maintaining homeostasis has been studied extensively. Although inflammasome-mediated inflammation and cell death are vital to limit pathogenic insults and to promote wound healing/tissue regeneration, unchecked/uncontrolled inflammation, and cell death can cause cytokine storm, tissue damage, autoinflammatory and autoimmune diseases, and even death in the afflicted individuals. NLRP3 is one of the major cytosolic sensors that assemble an inflammasome. Given the adverse consequences of uncontrolled inflammasome activation, our immune system has developed tiered mechanisms to inhibit NLRP3 inflammasome activation. In this review, we highlight and discuss recent advances and our current understanding of mechanisms by which NLRP3 inflammasome can be negatively regulated.

NLRP3 inflammasome activation is associated with PM2.5‐induced cardiac functional and pathological injury in mice

“…11 According to the reports, activation of caspase-1 led to the maturation and secretion of IL-1β and IL-18, which were regarded as the main players in initiating inflammatory response via NLRP3 inflammasome activation signaling axis. 11,19,20,40 The result that PM 2.5 increased the protein expression of Cleaved IL-1β, the key downstream factor of NLRP3 inflammasome activation, further confirmed the view that PM 2.5 activated NLRP3 inflammasome in cardiac tissues. After all, stimulus signal converted pro-IL-1β into Cleaved IL-1β, which depended on the assembly and activation of NLRP3 inflammasome.…”

“…Subsequently, caspase‐1 precursor (pro‐caspase‐1) is activated into Cleaved caspase‐1 with the formation of p10 and p20 . Meanwhile, active caspase‐1 converts the cytokines pro‐IL‐1β and pro‐IL‐18 into mature and biologically active IL‐1β and IL‐18, triggering the inflammation occurrence . Thus, the assembly of NLRP3 inflammasome, the induction of Cleaved caspase‐1 and Cleaved IL‐1β are regarded as the important symbols of NLRP3 inflammasome activation …”

“…[16][17][18] Meanwhile, active caspase-1 converts the cytokines pro-IL-1β and pro-IL-18 into mature and biologically active IL-1β and IL-18, triggering the inflammation occurrence. 19,20 Thus, the assembly of NLRP3 inflammasome, the induction of Cleaved caspase-1 and Cleaved IL-1β are regarded as the important symbols of NLRP3 inflammasome activation. 11 To date, it has been demonstrated that active NLRP3 inflammasome is involved in the inflammatory response of respiratory system induced by particulate matter.…”

Prdx4 limits caspase‐1 activation and restricts inflammasome‐mediated signaling by extracellular vesicles

“…He et al, 2016), yet little is known about endogenous factors that negatively regulate caspase-1 activity and thus may limit the proinflammatory cascade (Poudel & Gurung, 2018). Black arrows at 250 kDa indicate the corresponding molecular weights of rCASP-1 and rPRDX4 oligomers and decrease of the Prdx4 band intensity upon co-incubation with rCASP-1.…”

Allergic asthma: RIPK2 takes the lead

“…4 Several studies have shown an important role for these NLRs in regulating lung inflammation. 5 However, the role of these cytoplasmic sensors in the development of allergic asthma remain poorly understood.…”