Figure 1.

Classical pathways for NLRP3 inflammasome activation. Upon stimulation of TLR4, IL-1R or TNFR, TNF receptor-associated factor 2 (TRAF2) and TNF receptor-associated factor 6 (TRAF6) recruit the inhibitor of nuclear factor-κB kinase α/β (IKKα/β) that drives the translocation of NF-κB subunits to the nucleus. This upregulates the transcription of NLRP3 and pro-IL-1β, which enables the following assembly of NLFPR3 inflammasome initiated by various PAMPs and DAMPs. Once activated, the dormant procaspase-1 is cleaved into active caspase-1, which initiates the processing of gasdermin D, pro-IL-1β and pro-IL-18 to their biologically active forms.