Intracellular innate immunity in gouty arthritis: role of NALP3 inflammasome

Abstract

Gout is an inflammatory disease caused by the deposition of monosodium urate (MSU) crystals in the joint. Recent studies have significantly advanced our knowledge on the understanding of mechanisms underlying MSU crystal-induced inflammation. MSU crystals act as a 'danger signal' that can be recognized by pattern recognition receptors both at cell surface and cytoplasm, indicating the importance of innate immunity in gout. This review focuses on the critical role of intracellular NALP3 inflammasome in MSU crystal-induced inflammation.

Figure 1

Monosodium urate (MSU) crystal-induced activation of interleukin (IL)-1β by NALP3 inflammasome. MSU crystals are initially recognized at the cell surface by CD14, TLR2 and TLR4 that leads to synthesis of pro-IL-1β. Once MSU crystals are taken up into the cytoplasm, they can engage NALP3 probably through the LRR domain. This results in assembly of NALP3 inflammasome that leads to trigger caspase-1 activation, promote processing of pro-IL-1β and release of mature IL-1β.