J Rheum Dis 2022; 29(3): 140-153  
The Mechanism of the NLRP3 Inflammasome Activation and Pathogenic Implication in the Pathogenesis of Gout
Seong-Kyu Kim, M.D., Ph.D.
Division of Rheumatology, Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
Correspondence to: Seong-Kyu Kim, http://orcid.org/0000-0002-7780-0167
Division of Rheumatology, Department of Internal Medicine, Arthritis and Autoimmunity Research Center, Daegu Catholic University School of Medicine, 33 Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. E-mail: kimsk714@cu.ac.kr
Received: February 2, 2022; Revised: February 16, 2022; Accepted: February 22, 2022; Published online: July 1, 2022.
© Korean College of Rheumatology.

This is a open Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
The NACHT, LRR, and PYD-domains-containing protein 3 (NLRP3) inflammasome is an intracellular multi-protein signaling platform that is activated by cytosolic pattern-recognition receptors such as NLRs against endogenous and exogenous pathogens. Once it is activated by a variety of danger signals, recruitment and assembly of NLRP3, ASC, and pro-caspase-1 trigger the processing and release of pro-inflammatory cytokines including interleukin-1β (IL-1β) and IL-18. Multiple intracellular and extracellular structures and molecular mechanisms are involved in NLRP3 inflammasome activation. Gout is an autoinflammatory disease induced by inflammatory response through production of NLRP3 inflammasome-mediated proinflammatory cytokines such as IL-1β by deposition of monosodium urate (MSU) crystals in the articular joints and periarticular structures. NLRP3 inflammasome is considered a main therapeutic target in MSU crystal-induced inflammation in gout. Novel therapeutic strategies have been proposed to control acute flares of gouty arthritis and prophylaxis for gout flares through modulation of the NLRP3/IL-1 axis pathway. This review discusses the basic mechanism of NLRP3 inflammasome activation and the IL-1-induced inflammatory cascade and explains the NLRP3 inflammasome-induced pathogenic role in the pathogenesis of gout.
Keywords: NLRP3, Inflammasome, Gout, Interleukin-1, Monosodium urate

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