Fig. 2.

Mechanisms of NLRP3 inflammasome-driven IL-1β release

IL-1β release is regulated in two-steps: Transcriptional synthesis of pro-IL-1β and proteolytic processing into its mature form by inflammasomes. The transcriptional regulation of IL-1β mRNA is mediated by TLRs and IL-1 receptor (signal 1), which also provides NLRP3 mRNA. Then, the NLRP3 inflammasome-activated caspase-1 processes accumulated pro-IL-1β and induces the release of IL-1β (signal 2). The common upstream pathways of NLRP3 inflammasomes include potassium efflux, generation of mitochondrial ROS, and lysosomal destabilization and leakage of cathepsin B. Activated caspase-1 also cleaves GSDMD, whose processed N-terminal fragment (GSDMD-N) increases plasma membrane permeability, resulting in pyroptosis. ROS, reactive oxygen species; TLRs, Toll-like receptors.