Fig. 2.

Canonical activation of the NLRP3 inflammasome pathways. NLRP3 canonical activation requires two steps, a priming step and an activation step.The priming is achieved through the identification of pathogen-associated molecular patterns and damage-associated molecular patterns. TNF, IL-1, HMGB1, IFN, TGF-1β and LPS could upregulate NLRP3 expression by inducing nuclear NF-κB activation.Primed NLRP3 induces inflammasome assembly and full activation upon recognition of K + efflux, Cl − efflux, Ca2 + mobilization, lysosome destruction, anti-Golgi dissociation, mitochondrial dysfunction, mitochondrial ROS production and mitochondrial DNA release into the cytosol.NLRP3 inflammasome formation includes binding of NLRP3 with NEK7, oligomerization of NLRP3, assembly of ASCs into fibrils, and recruitment and activation of Caspase 1. Actived NLRP3 inflammasome can induce caspase-1-dependent pyroptosis in host cells. Active GSDMD, which bind to phosphatidylinositol phosphates and phosphatidyl serine in the membrane leaflets, aggregate and insert into the plasma membrane to form a pore. Inflammatory cytokines such as IL-1β and IL-18 are released into the interstitial space and activate corresponding receptors in adjacent cells, causing an immune cascade and amplifying the injury effect