Composition of the NALP3 inflammasome and its activation by monosodium urate. Phagocytosis of monosodium urate (MSU) crystals leads to the generation of reactive oxygen species (ROS) through activation of NADPH oxidases. This event activates the NLRP3 inflammasome. MSU crystals may also induce the secretion of ATP, which in turn activates P2X7R. On activation of the P2X7 receptor, there is rapid exit of intracellular potassium that triggers the NLRP3 inflammasome. A rise in intracellular calcium is also required for the secretion of processed IL-1β. The macromolecular complex (inflammasome) consists of NLRP3, ASC and procaspase-1, and CARDINAL. Assembly leads to activation of caspase-1, which in turn cleaves pro-IL-1β to produce biologically active IL-1β. ASC, apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD); FIIND, domain with function to find; LRR, leucine-rich repeat; MDP, muramyl dipeptide; NACHT, domain conserved in NAIP, CIITA, HET-E and TP1; NALP3, NACHT-containing, LRR-containing and PYD-containing protein; PYD, pyrin death domain.
Busso and So Arthritis Research & Therapy 2010 12:206 doi:10.1186/ar2952