UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Date

1-13-2017

Document Type

Article

Disciplines

Immunity | Nephrology

Abstract

Uric acid is a damage-associated molecular pattern (DAMP), released from ischemic tissues and dying cells which, when crystalized, is able to activate the NLRP3 inflammasome. Soluble uric acid (sUA) is found in high concentrations in the serum of great apes, and even higher in some diseases, before the appearance of crystals. In the present study, we sought to investigate whether uric acid, in the soluble form, could also activate the NLRP3 inflammasome and induce the production of IL-1beta. We monitored ROS, mitochondrial area and respiratory parameters from macrophages following sUA stimulus. We observed that sUA is released in a hypoxic environment and is able to induce IL-1beta release. This process is followed by production of mitochondrial ROS, ASC speck formation and caspase-1 activation. Nlrp3-/- macrophages presented a protected redox state, increased maximum and reserve oxygen consumption ratio (OCR) and higher VDAC protein levels when compared to WT and Myd88-/- cells. Using a disease model characterized by increased sUA levels, we observed a correlation between sUA, inflammasome activation and fibrosis. These findings suggest sUA activates the NLRP3 inflammasome. We propose that future therapeutic strategies for renal fibrosis should include strategies that block sUA or inhibit its recognition by phagocytes.

Rights and Permissions

Copyright © 2017, The Author(s). Citation: Sci Rep. 2017 Jan 13;7:39884. doi: 10.1038/srep39884. Link to article on publisher's site

DOI of Published Version

10.1038/srep39884

Related Resources

Link to Article in PubMed

Journal Title

Scientific reports

PubMed ID

28084303

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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