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. 2021 Mar 8;5:18. doi: 10.1038/s41698-021-00154-7

Fig. 1. Mechanisms of conventional inflammasome activation and alternative inflammasome activation in tumor microenvironment.

Fig. 1

Conventional inflammasome activation process comprises two main signals: Signal 1, which is induced by PRRs such as Toll-like receptors activated by PAMPs such as bacterial lipopolysaccharide (LPS). This leads to the transcriptional upregulation of IL1B, and IL18 via NF-κB signaling. Signal 2 is provided by PAMPs or DAMPs, such as ATP and crystals (e.g., asbestos, silica, or uric acid), which activates signaling events including K+ efflux, reactive oxygen species (ROS), and lysosomal damage, leading to activation and recruitment of NLRP3 oligomerization and formation of NLRP3 inflammasome complex. The activation and formation of NLRP3 inflammasome provoke auto-cleavage of the active caspase-1, which then proteolytically cleaves pro-IL-1β and pro-IL-18 into their bioactive forms IL-1β and IL-18. Alternatively, the inflammasomes can be activated by cancer cell-derived soluble factors (e.g., TGF-β, sCD44, and WNT ligand), ATP from dying tumor cells, and UV in tumor microenvironment. This alternative activation of inflammasome can also include maturation and secretion of IL-1β and IL-18 in tumor microenvironment.