Fig. 1.

Mechanisms of NLRP3 inflammasome assembly and activation. NLRP3 needs to be primed prior to activation. The priming process includes the binding of PAMPs/DAMPs to TLR or CD36, which promotes the transcription of NLRP3 and IL-1β. The priming event also includes de-ubiquitination of NLRP3. The ubiquitination and phosphorylation of the adaptor protein ASC is also necessary for the assembly of inflammasome. Disruption of the lysosome and release of cathepsin enhances the activation of NLRP3 inflammasome. The assembly of activated inflammasome leads to the processing of pro-caspase-1 into mature and active enzyme, which in turn cleaves pro-IL-1β and pro-IL-18 into active cytokines. Inset: activated NLRP3 binds to ASC through PYD–PYD interactions. Pro-caspase-1 binds to ASC through CARD–CARD interactions