UMMS Affiliation

Division of Infectious Diseases and Immunology, Department of Medicine

Publication Date

2021-02-05

Document Type

Article

Disciplines

Endocrine System Diseases | Immunology and Infectious Disease | Nutritional and Metabolic Diseases

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-1beta (IL-1beta) 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-1beta 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.

Keywords

NOD-like receptors, Endocrine system and metabolic diseases

Rights and Permissions

© The Author(s) 2021 Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

DOI of Published Version

10.1038/s41419-021-03445-w

Source

Braga TT, Davanso MR, Mendes D, de Souza TA, de Brito AF, Cruz MC, Hiyane MI, de Lima DS, Nunes V, de Fátima Giarola J, Souto DEP, Próchnicki T, Lauterbach M, Biscaia SMP, de Freitas RA, Curi R, Pontillo A, Latz E, Camara NOS. Sensing soluble uric acid by Naip1-Nlrp3 platform. Cell Death Dis. 2021 Feb 5;12(2):158. doi: 10.1038/s41419-021-03445-w. PMID: 33547278; PMCID: PMC7864962. Link to article on publisher's site

Journal/Book/Conference Title

Cell death and disease

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

33547278

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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