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

Ana Carolina Matias Dinelly Pinto, Rodolfo de Melo Nunes, Igor Albuquerque Nogueira, Bernhard Fischer, Rudolf Lucas, Virgínia Claudia Carneiro Girão-Carmona, Vivian Louise Soares de Oliveira, Flavio Almeida Amaral, Georg Schett, Francisco Airton Castro Rocha

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number1049368
JournalFrontiers in immunology
Volume13
DOIs
StatePublished - Oct 31 2022

Keywords

  • arthritis
  • cytokines
  • inflammation
  • neutrophils
  • tumor necrosis factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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