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. 2010 Jun;120(6):1809-11.
doi: 10.1172/JCI43132. Epub 2010 May 24.

Caught red-handed: uric acid is an agent of inflammation

Yan Shi  1
Affiliations

Caught red-handed: uric acid is an agent of inflammation

Yan Shi. J Clin Invest. 2010 Jun.

Abstract

Inflammation occurs in response to both pathogenic insult and tissue damage under sterile conditions, with the latter contributing to the pathogenesis of many diseases. Although several endogenous substances, including uric acid, have been suggested to alert the body to danger and to stimulate inflammation, little is known about their contribution to such responses in vivo. In this issue of the JCI, Kono et al. use newly generated mice with reduced levels of uric acid to investigate its role as an endogenous signal of tissue damage in inflammatory responses to hepatic injury. They find that uric acid is released from dying tissues and induces inflammation to cell death but is not involved in the response to microbial molecules or sterile irritant particles. I believe this to be the first report of an endogenous danger signal acting as a physiological regulator of inflammation.

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Figures

Figure 1
Figure 1. Proposed mechanism by which uric acid triggers inflammation.
Tissue damage of various forms produces and releases uric acid from purines via xanthine oxidase. Uric acid in the extracellular environment binds to sodium to form MSU. With assistance from serum factors, such as MSU-binding antibodies, MSU crystals precipitate. The crystals engage APC membrane lipids to trigger phagocytosis and APC activation. MSU gains entry into the cell where it interacts with the NLRP3 inflammasome to produce IL-1β. IL-1β signals via its receptor (IL-1R) on parenchymal cells, and along with other chemotactic factors, it serves as a beacon to attract neutrophils and other immune cells, thereby eliciting an inflammatory response to tissue injury.
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  • J Clin Invest. 120:1939.

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