Figure 1.

Schematic diagram of the molecular mechanism of NLRP3 inflammasome priming and activation. The priming steps of NLRP3 are regulated by TLR, FADD, caspase-8, and NOD1/2, which facilitate the activation of NF-κB and induce the activation of NLRP3. Canonical conditions of NLRP3 inflammasome oligomerization and activation include ATP, P2X7R, lysosomal damage, cathepsin release, K⁺ outflow, mitochondrial ROS damage, etc. On the one hand, activated caspase-1 cleaves GSDMD into a lipophilic N-terminal soluble in the cytoplasm and a hydrophilic C-terminal that can be embedded into the cell membrane. The GSDMD-N terminal domain will combine with the phospholipids on the cell membrane to form holes and induce pyroptosis. On the other hand, activated caspase-1 releases inflammatory cytokines such as IL-1β and IL-18. Non-canonical NLRP3 inflammasome activation is mediated by caspase-4, caspase-5, and caspase-11. By Figdraw.