Figure 2.

Mechanisms of inflammasome activation. Inflammasome activation in general relies on two signals for its activation. First, a PAMP binds to a PRR resulting in synthesis of NLRP3 and pro-IL-1β. Then a second signal leads to inflammasome assembly, leading to the activation of caspase-1, processing of pro-IL-1β into IL-1β and pyroptosis. The second signal may come from a variety of pathways including K⁺ efflux. Lysosomal rupture or mitochondrial dysfunction. Mitochondrial dysfunction results in release of ROS, Ca²⁺ and mitochondrial DNA (mtDNA), all of which have been shown to activate the inflammasome. Pyroptosis occurs as a result of caspase-1-mediated cleavage of GSDM-D at the linker region of GSDM-D. Following GSDM-D cleavage, the amino terminus of GSDM-D (GSDM-D-N) forms a non-selective pore at the cell membrane through which IL-1β is then released.