Figure 1.

The NLRP3 inflammasome and IL-1β processing and secretion in crystal-induced inflammation. The figure shows monosodium urate crystal interaction with phagocytes, with crystal recognition at the macrophage surface mediated by innate immune mechanisms, in part employing Toll-like receptor (TLR)2 and TLR4 and associated MyD88 signaling, Fc receptors, and integrins. Crystal uptake with consequent phagolysosome destabilization, and reactive oxygen species generation and lowering of cytosolic K⁺ all appear to promote activation of the NLRP3 (cryopyrin) inflammasome. Consequent endoproteolytic activation of caspase-1, which drives pro-IL-1β maturation, and consequent secretion of mature IL-1β is a major mechanism stimulating experimental gouty inflammation, and appears to be implicated in human gouty arthritis, as discussed in the text.