title: The role of uric acid as an endogenous danger signal in immunity and inflammation.
abstract: Gout is an ancient disease that still plagues us. Its pathogenic culprit, uric acid crystal deposition in tissues, is a strong inflammatory stimulant. In recent years, the mechanisms through which uric acid crystals promote inflammation have been a subject of increasing interest among rheumatologists and immunologists. Uric acid has been identified as an endogenous adjuvant that drives immune responses in the absence of microbial stimulation. Because uric acid is a ubiquitous metabolite that is produced in high quantities upon cellular injury, the ramifications of its effects may be considerable in health and in disease. Uric acid crystals also have been shown to trigger interleukin-1β-mediated inflammation via activation of the NOD-like receptor protein (NLRP)3 inflammasome, a multimolecular complex whose activation appears to be central to many pathological inflammatory conditions. In this article, we review the possible mechanisms of uric acid-mediated inflammation and offer some historical perspectives on what has been learned about the complex effects of a relatively simple substance.
authors.affiliation: Department of Microbiology and Infectious Disease and Immunology Research Group, University of Calgary, 4A18 HRIC, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Faranak
authors.initials: F
authors.lastname: Ghaemi-Oskouie
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism; D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D002352:Carrier Proteins / Q000378:metabolism; D003460:Crystallization; D004195:Disease Models, Animal; D006073:Gout / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D014527:Uric Acid / Q000276:immunology* / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D014527:Uric Acid