Soluble Uric Acid Activates the NLRP3 Inflammasome

Overview

Journal Sci Rep

Specialty Science

Date 2017 Jan 14

PMID 28084303

Citations 164

Authors

Tarcio Teodoro Braga

Maria Fernanda Forni

Matheus Correa-Costa

Rodrigo Nalio Ramos

Jose Alexandre Barbuto

Paola Branco

Angela Castoldi

Meire Ioshie Hiyane

Mariana Rodrigues Davanso

Eicke Latz

Bernardo S Franklin

Alicia J Kowaltowski

Niels Olsen Saraiva Camara

Affiliations

Soon will be listed here.

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-1β. 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-1β 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.

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