Soluble Uric Acid Activates the NLRP3 Inflammasome

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dc.citation.volume7
dc.contributor.authorBraga, Tarcio Teodoro
dc.contributor.authorForni, Maria Fernanda
dc.contributor.authorCorrea-Costa, Matheus
dc.contributor.authorRamos, Rodrigo Nalio
dc.contributor.authorBarbuto, Jose Alexandre
dc.contributor.authorBranco, Paola
dc.contributor.authorCastoldi, Angela
dc.contributor.authorHiyane, Meire Ioshie
dc.contributor.authorDavanso, Mariana Rodrigues
dc.contributor.authorLatz, Eicke
dc.contributor.authorFranklin, Bernardo S.
dc.contributor.authorKowaltowski, Alicia J.
dc.contributor.authorSaraiva Camara, Niels Olsen [UNIFESP]
dc.coverageLondon
dc.date.accessioned2020-07-17T14:03:15Z
dc.date.available2020-07-17T14:03:15Z
dc.date.issued2017
dc.description.abstractUric 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-1 beta. 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-1 beta 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.en
dc.description.affiliationUniv Sao Paulo, Lab Transplantat Immunobiol, Dept Immunol, Inst Biomed Sci 4, Sao Paulo, Brazil
dc.description.affiliationUniv Bonn, Univ Hosp, Inst Innate Immun, Bonn, Germany
dc.description.affiliationUniv Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Lab Tumor Immunol, Dept Immunol, Inst Biomed Sci 4, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Dept Cellular Biol, Inst Biomed Sci, Sao Paulo, Brazil
dc.description.affiliationUniv Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA USA
dc.description.affiliationGerman Ctr Neurodegenerat Dis, Bonn, Germany
dc.description.affiliationNorwegian Univ Sci & Technol, Dept Canc Res & Mol Med, Ctr Mol Inflammat Res, Trondheim, Norway
dc.description.affiliationFed Univ Sao Paulo UNIFESP, Div Nephrol, Clin & Expt Immunol Lab, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Fac Med, Renal Pathophysiol Lab LIM16, Sao Paulo, Brazil
dc.description.affiliationUnifespFed Univ Sao Paulo UNIFESP, Div Nephrol, Clin & Expt Immunol Lab, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipCNPq (Fluid Complex INCT)
dc.description.sponsorshipSao Paulo Research Foundation (Fapesp)
dc.description.sponsorshipIDFAPESP: 2014/06992-8
dc.description.sponsorshipIDFAPESP: 2012/02270-2
dc.description.sponsorshipIDFAPESP: 2013/07937-8
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1038/srep39884
dc.identifier.citationScientific Reports. London, v. 7, p. -, 2017.
dc.identifier.doi10.1038/srep39884
dc.identifier.fileWOS000392160900001.pdf
dc.identifier.issn2045-2322
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55257
dc.identifier.wosWOS:000392160900001
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofScientific Reports
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleSoluble Uric Acid Activates the NLRP3 Inflammasomeen
dc.typeinfo:eu-repo/semantics/article
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