Sensing soluble uric acid by Naip1-Nlrp3 platform

Author(s):Show less -

Braga, Tarcio Teodoro ^{[1, 2, 3]} ; Davanso, Mariana Rodrigues ^{[2, 3, 4]} ; Mendes, Davi ^[5] ; de Souza, Tiago Antonio ^[5] ; de Brito, Anderson Fernandes ^[6] ; Cruz, Mario Costa ^[2] ; Hiyane, Meire Ioshie ^[2] ; de Lima, Dhemerson Souza ^[2] ; Nunes, Vinicius ^[2] ; Giarola, Juliana de Fatima ^[7] ; Pires Souto, Denio Emanuel ^{[7, 8]} ; Prochnicki, Tomasz ^[3] ; Lauterbach, Mario ^[3] ; Petris Biscaia, Stellee Marcela ^[9] ; de Freitas, Rilton Alves ^[8] ; Curi, Rui ^{[10, 4]} ; Pontillo, Alessandra ^[2] ; Latz, Eicke ^{[11, 3, 12]} ; Saraiva Camara, Niels Olsen ^{[13, 2, 14]}

Affiliation:Show less -

^[1] Univ Fed Parana, Dept Basic Pathol, Curitiba, Parana - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Sao Paulo, SP - Brazil

^[3] Univ Hosp Bonn, Inst Innate Immun, Bonn - Germany

^[4] Univ Sao Paulo, Inst Biomed Sci 1, Dept Physiol & Biophys, Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Inst Biomed Sci 2, Dept Microbiol, Sao Paulo, SP - Brazil

^[6] Imperial Coll London, Dept Life Sci, London SW7 2AZ - England

^[7] Univ Estadual Campinas, Inst Chem, Campinas, SP - Brazil

^[8] Univ Fed Parana, Dept Chem, Curitiba, Parana - Brazil

^[9] Univ Fed Parana, Dept Cellular Biol, Curitiba, Parana - Brazil

^[10] Cruzeiro do Sul Univ, Interdisciplinary Postgrad Program Hlth Sci, Sao Paulo - Brazil

^[11] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01655 - USA

^[12] Norwegian Univ Sci & Technol, Ctr Mol Inflammat Res CEMIR, N-7491 Trondheim - Norway

^[13] Univ Fed Sao Paulo, Nephrol Div, Sao Paulo, SP - Brazil

^[14] Univ Sao Paulo, Fac Med, Renal Physiopathol Lab, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: CELL DEATH & DISEASE; v. 12, n. 2 FEB 5 2021.
• Web of Science Citations: 0

Abstract

Uric acid (UA), a product of purine nucleotide degradation able to initiate an immune response, represents a breakpoint in the evolutionary history of humans, when uricase, the enzyme required for UA cleavage, was lost. Despite being inert in human cells, UA in its soluble form (sUA) can increase the level of interleukin-1 beta (IL-1 beta) in murine macrophages. We, therefore, hypothesized that the recognition of sUA is achieved by the Naip1-Nlrp3 inflammasome platform. Through structural modelling predictions and transcriptome and functional analyses, we found that murine Naip1 expression in human macrophages induces IL-1 beta expression, fatty acid production and an inflammation-related response upon sUA stimulation, a process reversed by the pharmacological and genetic inhibition of Nlrp3. Moreover, molecular interaction experiments showed that Naip1 directly recognizes sUA. Accordingly, Naip may be the sUA receptor lost through the human evolutionary process, and a better understanding of its recognition may lead to novel anti-hyperuricaemia therapies. (AU)

• FAPESP's process: 17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/06992-8 - Cellular, molecular and immunological mechanisms generated through NLRP activation
• Grantee: Tárcio Teodoro Braga
• Support Opportunities: Scholarships in Brazil - Post-Doctoral