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Potent anti-inflammatory activity of the lectin-like domain of TNF in joints

In view of the crucial role of tumor necrosis factor (TNF) in joint destruction, TNF inhibitors, including neutralizing anti-TNF antibodies and soluble TNF receptor constructs, are commonly used therapeutics for the treatment of arthropathies like rheumatoid arthritis (RA). However, not all patients...

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Detalles Bibliográficos
Autores principales: Pinto, Ana Carolina Matias Dinelly, Nunes, Rodolfo de Melo, Nogueira, Igor Albuquerque, Fischer, Bernhard, Lucas, Rudolf, Girão-Carmona, Virgínia Claudia Carneiro, de Oliveira, Vivian Louise Soares, Amaral, Flavio Almeida, Schett, Georg, Rocha, Francisco Airton Castro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9659759/
https://www.ncbi.nlm.nih.gov/pubmed/36389831
http://dx.doi.org/10.3389/fimmu.2022.1049368
Descripción
Sumario:In view of the crucial role of tumor necrosis factor (TNF) in joint destruction, TNF inhibitors, including neutralizing anti-TNF antibodies and soluble TNF receptor constructs, are commonly used therapeutics for the treatment of arthropathies like rheumatoid arthritis (RA). However, not all patients achieve remission; moreover, there is a risk of increased susceptibility to infection with these agents. Spatially distinct from its receptor binding sites, TNF harbors a lectin-like domain, which exerts unique functions that can be mimicked by the 17 residue solnatide peptide. This domain binds to specific oligosaccharides such as N′N′-diacetylchitobiose and directly target the α subunit of the epithelial sodium channel. Solnatide was shown to have anti-inflammatory actions in acute lung injury and glomerulonephritis models. In this study, we evaluated whether the lectin-like domain of TNF can mitigate the development of immune-mediated arthritis in mice. In an antigen-induced arthritis model, solnatide reduced cell influx and release of pro-inflammatory mediators into the joints, associated with reduction in edema and tissue damage, as compared to controls indicating that TNF has anti-inflammatory effects in an acute model of joint inflammation via its lectin-like domain.