Year: 2021
Type: article
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-1β (IL-1β) 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-1β 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.
Source: Cell Death and Disease
Authors: Tarcio Teodoro Braga, Mariana Rodrigues Davanso, Davi Mendes, Tiago Antonio de Souza, Anderson Fernandes de Brito, Mario Costa Cruz, Meire Ioshie Hiyane, Dhemerson Souza de Lima, Vinicius Nunes, Juliana de Fátima Giarola, Denio Emanuel Pires Souto, Tomasz Próchnicki, Mario Lauterbach, Stellee Marcela Petris Biscaia, Rilton Alves de Freitas, Rui Curi, Alessandra Pontillo, Eicke Latz, Niels Olsen Saraiva Camara
Institutions: Universidade de São Paulo, University Hospital Bonn, Universidade Federal do Paraná, Imperial College London, Universidade Estadual de Campinas (UNICAMP), Universidade Cruzeiro do Sul, University of Massachusetts Chan Medical School, Norwegian University of Science and Technology, Universidade Federal de São Paulo
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,170
Funders: Norges Teknisk-Naturvitenskapelige Universitet, Imperial College London, Deutsche Forschungsgemeinschaft, Fundação de Amparo à Pesquisa do Estado de São Paulo, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Universidade de São Paulo, National Institutes of Health, National Heart, Lung, and Blood Institute
OpenAlex ID: W3126269755