Fig. 2.

Mechanisms of inflammasome assembly and pyroptosis. The inflammasome is activated by two consecutive signals. First, PAPM or DAMP initiates some pathways through PRR, mainly TLR4 that leads to an increase in the expression of NF-kβ in the nucleus. The NF-kβ triggers the production of Pro-IL-1β and Pro-IL18. The second signal is initiated by potassium efflux, lysosomal rupture, and P2X7 receptors and mitochondrial dysfunctions due to depletion of calcium reserves as well as the release of Mitochondrial DNA (MtDNA) and ROS into the cytosol. These changes create inflammasome components (i.e., NLRP3, ASC, and activated caspase-1). Activated caspase-1 cleavages the linker region of gasdermin-D and forms a pore in the cellular membrane. In addition, caspase-1 changes Pro-IL-1β and Pro-IL18 into the activated forms. Finally, these proinflammatory cytokines released into the extracellular by pores called pyroptosis. Abbreviations: ASC adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain; DAMP damage-associated molecular pattern; IL-1β interleukin 1beta; IL-18 interleukin18; mt DNA mitochondrial DNA; NF-kβ nuclear factor-kappa B; NLRP3 nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3; P2X7 purinergic type 2 ATP receptor family; PAMP pathogen-associated molecular pattern; PRR pattern recognition receptor; ROS reactive oxygen species; TLR4 toll-like receptor 4