| Literature DB >> 33547278 |
Eicke Latz1,2,3, Niels Olsen Saraiva Camara4,5,6, Tarcio Teodoro Braga7,8,9, Mariana Rodrigues Davanso4,1,10, Davi Mendes11, Tiago Antonio de Souza11, Anderson Fernandes de Brito12, Mario Costa Cruz4, Meire Ioshie Hiyane4, Dhemerson Souza de Lima4, Vinicius Nunes4, Juliana de Fátima Giarola13, Denio Emanuel Pires Souto13,14, Tomasz Próchnicki1, Mario Lauterbach1, Stellee Marcela Petris Biscaia15, Rilton Alves de Freitas14, Rui Curi10,16, Alessandra Pontillo4.
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.Entities:
Year: 2021 PMID： 33547278 PMCID： PMC7864962 DOI： 10.1038/s41419-021-03445-w
Source DB: PubMed Journal: Cell Death Dis Impact factor: 8.469