FIGURE 1.

The structure and activation of NLRP3 inflammasome: NLRP3 inflammasome consists of NLRP3, ASC, and pro-caspase-1. A two-step mechanism leads to NLRP3 inflammasome activation, including the priming and the activation step. During the priming step, TLR, NOD2, or TNFR receives the stimulation induced by extracellular signaling molecules, leading to the activation of NF-κB. NF-κB then promotes the expression of NLRP3, pro-IL-1β, and pro-IL-18. During the activation step, the stimulation like K⁺ efflux, Ca²⁺ mobilization, Na⁺ influx, chloride efflux, ROS, mitochondrial dysfunction, and lysosomal damage leads to the assembly of NLRP3 inflammasome. In the process of NLRP3 inflammasome activation, activated caspase-1 transforms pro-IL-1β and pro-IL-18 into mature IL-1β and IL-18, resulting in the release of inflammatory cytokines. Further, activated caspase-1 dissociates GSDMD to release its N-terminus, form pores in the plasma membrane, and stimulate the occurrence of pyroptosis. ASC, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (CARD); GSDMD, gasdermin D; NF-κB, nuclear factor-κB; NLRP3, nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3; pro-IL-1β, pro-interleukin-1β; pro-IL-18, pro-interleukin-18; ROS, reactive oxygen species; TLR, toll-like receptor; TNFR, tumor necrosis factor receptor.