TY - JOUR
T1 - Potent anti-inflammatory activity of the lectin-like domain of TNF in joints
AU - Pinto, Ana Carolina Matias Dinelly
AU - Nunes, Rodolfo de Melo
AU - Nogueira, Igor Albuquerque
AU - Fischer, Bernhard
AU - Lucas, Rudolf
AU - Girão-Carmona, Virgínia Claudia Carneiro
AU - de Oliveira, Vivian Louise Soares
AU - Amaral, Flavio Almeida
AU - Schett, Georg
AU - Rocha, Francisco Airton Castro
N1 - Publisher Copyright:
Copyright © 2022 Pinto, Nunes, Nogueira, Fischer, Lucas, Girão-Carmona, de Oliveira, Amaral, Schett and Rocha.
PY - 2022/10/31
Y1 - 2022/10/31
N2 - 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.
AB - 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.
KW - arthritis
KW - cytokines
KW - inflammation
KW - neutrophils
KW - tumor necrosis factor
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U2 - 10.3389/fimmu.2022.1049368
DO - 10.3389/fimmu.2022.1049368
M3 - Article
C2 - 36389831
AN - SCOPUS:85141955678
SN - 1664-3224
VL - 13
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 1049368
ER -