Silica particles activate the inflammasome and induce IL-1 production. Phagocytosis of silica particles leads to phagosomal damage and activation of NALP3. Then, NALP3 associates with the intracellular apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) that activates pro-caspase-1. The resulting inflammasome then cleaves pro-IL-1β to proinflammatory IL-1β. Binding of silica to the cell membrane can also induce secretion of IL-1β without lysosomal damage. Silica activates the NALP3 inflammasome that results in the efflux of potassium ions, suggesting an interaction of silica with a membrane-associated protein. Secretion of IL-1β and TNF-α leads to a positive feedback loop via IL-1 receptor signaling and additionally induces the production of IL-6. NALP3, NACHT, LRR, and PYD domains-containing protein 3; ASC, apoptosis-associated speck-like protein containing a caspase recruitment domain; NF-κB, nuclear factor-κB; IL, interleukin. This figure was created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://smart.servier.com, accessed on 7 June 2022.