Fig. 2

Mechanisms of NLRP3 inflammasome-driven IL-1β release. IL-1β release is regulated by a two-step regulation: transcriptional synthesis of pro-IL-1β and proteolytic processing into its mature form by the inflammasomes. The transcriptional regulation of IL-1β mRNA is mediated by TLRs and IL-1 receptor (signal 1), which also induces NLRP3 mRNA expression. Then, NLRP3 inflammasomes induce caspase-1 activation and the subsequent conversion of pro-IL-1β to its mature form (signal 2). As common upstream pathways of NLRP3 inflammasomes, three mechanisms are known: (1) potassium efflux, (2) generation of mitochondrial ROS, and (3) lysosomal destabilization and leakage of cathepsin B. Activated caspase-1 also cleaves GSDMD, whose processed N-terminal fragment (GSDMD-N) forms plasma membrane pores to increase membrane permeability, resulting in pyroptosis