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. 2020 Jul 13;10(10):1880–1903. doi: 10.1016/j.apsb.2020.07.003

Figure 4.

Figure 4

Lysosome and pyroptosis. In pyroptosis, lysosomal rupture can be initiated by various crystalline materials, nano-particles, chemical compounds, rare earth oxide, and maybe ROS. Subsequent CatB release and K+ efflux activate NLRP3 inflammasome. But in pyroptosis induced by the endocytosis of HMGB1, lysosome destabilization and CatB release are necessary for pyroptosome formation. Activated NLRP3 inflammasome or pyroptosome stimulates caspase-1. CatB can be inhibited by Ca074Me, endogenous cystatin C, or genetic knockout of CatB. Lysosome destabilization caused by HMGB1 is also indispensable for LPS-induced activation of non-canonical inflammasome and caspase-11, since it allows LPS internalized through HMGB1–RAGE signaling pathway to escape from lysosomal degradation. Activated caspase-1 and -11 drive the cleavage of pro-IL-1β/18 and GSDMD, coordinating membrane lysis, mature IL-1β/18 release and ultimate pyroptosis. CatB: cathepsin B.