Figure 1 Activation and signalling of IL-1 Figure 1 | Activation and signalling of IL-1. Release of IL-1β from monocytes/macrophages and neutrophils requires enzymatic processing of its intracellular precursor protein (pro-IL-1β). This step can occur by two different pathways. Caspase-1-mediated cleavage of pro-IL-1β depends on the activation of an intracellular protein complex called the inflammasome (inflammasome-dependent IL-1β activation). The inflammasome is induced by damage-associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPS) such as uric acid crystals, double-stranded DNA (dsDNA) or ATP. Alternatively, pro-IL-1β can be cleaved by neutrophil-derived serine proteases in a process independent of inflammasome activation. IL-1α is produced and localized intracellularly (for example, in epithelial cells). In the event of cell necrosis, IL-1α is released and acts as an alarmin. IL-1α and IL-1β bind to IL-1 receptor type 1 (IL-1R1) on target cells, engaging IL-1 receptor accessory protein (IL-1RAcP) and leading to activation of IL-1 receptor-associated kinase 4 (IRAK4) and NFκB, which, in turn, induce the transcription of IL-1 target genes. Soluble IL-1 receptor antagonist (IL-1Ra) and membrane-bound or soluble IL-1 receptor type 2 (IL-1R2) are negative regulators of the IL-1 pathway. dsRNA, double-strand RNA; ILC3, innate lymphoid cell type 3; MMP, matrix metalloproteinase; PGE2, prostaglandin E2; RANKL, receptor-activator of NFκB ligand, also known as TNF ligand superfamily member 11; TH17, T helper 17. Schett, G. et al. (2015) Interleukin‑1 function and role in rheumatic disease Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2016.166