Dysregulated serum IL-23 and SIRT1 activity in peripheral blood mononuclear cells of patients with rheumatoid arthritis.
Fiche publication
Date publication
janvier 2015
Journal
PloS one
Auteurs
Membres identifiés du Cancéropôle Est :
Pr HERBEIN Georges, Pr TOUSSIROT Eric
Tous les auteurs :
Wendling D, Abbas W, Godfrin-Valnet M, Kumar A, Guillot X, Khan KA, Vidon C, Coquard L, Toussirot E, Prati C, Herbein G
Lien Pubmed
Résumé
Sirtuin 1 (Sirt1) is a class III histone deacetylase (HDAC) that modulates gene expression and is involved in the regulation of proinflammatory cytokines. Interleukin-23 (IL-23) is produced by activated macrophages and dendritic cells and could fuel the progression of rheumatoid arthritis (RA). The goal of our study was to evaluate serum IL-23 levels and both Sirt1 activity and expression in peripheral blood mononuclear cells (PBMCs) in patients with RA compared to healthy controls (HC) and to determine the relationship between Sirt1 activity/expression and IL-23 levels. We assessed apoptosis in PBMCs of RA patients and its association with Sirt1 expression and serum IL-23. Serum IL-23 levels were increased in RA patients in comparison with controls. We found a positive correlation between the levels of serum IL-23 and serum IL-6 in RA patients. Decreased cytoplasmic Sirt1 activity was observed in RA patients with severe disease compared to HC. The expression of Sirt1 protein was significantly decreased in PBMCs of RA patients compared to HC using western blotting. Serum IL-23 levels correlated positively with the cytoplasmic Sirt1 activity in RA patients. Apoptosis rate of PBMCs isolated from RA patients was increased compared to HC and correlated negatively with the expression of Sirt1 protein and serum IL-23 levels. Levels of serum IL-23 and Sirt1 activity and expression were disturbed in RA parallel to increased PBMC apoptosis. Our findings might provide the rationale for the development of new therapeutic approaches in RA.
Mots clés
Apoptosis, Arthritis, Rheumatoid, blood, Biomarkers, blood, Case-Control Studies, Disease Progression, Female, Humans, Interleukin-23 Subunit p19, blood, Interleukin-6, blood, Leukocytes, Mononuclear, metabolism, Male, Middle Aged, Sirtuin 1, blood
Référence
PLoS ONE. 2015 ;10(3):e0119981