UMMS Affiliation
Department of Medicine, Division of Infectious Diseases and Immunology
Publication Date
2017-01-13
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).
DOI of Published Version
10.1038/srep39884
Source
Sci Rep. 2017 Jan 13;7:39884. doi: 10.1038/srep39884. Link to article on publisher's site
Journal/Book/Conference Title
Scientific reports
Related Resources
PubMed ID
28084303
Repository Citation
Braga, Tarcio Teodoro; Forni, Maria Fernanda; Correa-Costa, Matheus; Ramos, Rodrigo Nalio; Barbuto, Jose Alexandre; Branco, Paola; Castoldi, Angela; Hiyane, Meire Ioshie; Davanso, Mariana Rodrigues; Latz, Eicke; Franklin, Bernardo S.; Kowaltowski, Alicia J.; and Camara, Niels Olsen Saraiva, "Soluble Uric Acid Activates the NLRP3 Inflammasome" (2017). Open Access Articles. 3066.
https://escholarship.umassmed.edu/oapubs/3066
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.