title: Dysregulated serum IL-23 and SIRT1 activity in peripheral blood mononuclear cells of patients with rheumatoid arthritis.
abstract: 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.
authors: Department of Rheumatology, Centre Hospitalier Régional Universitaire, Besançon, France; Pathogens & Inflammation Laboratory, University of Franche-Comté, Besançon, France.
authors: Daniel
authors: D
authors: Wendling
authors: Pathogens & Inflammation Laboratory, University of Franche-Comté, Besançon, France.
authors: Wasim
authors: W
authors: Abbas
authors: Department of Rheumatology, Centre Hospitalier Régional Universitaire, Besançon, France.
authors: Marie
authors: M
authors: Godfrin-Valnet
authors: Pathogens & Inflammation Laboratory, University of Franche-Comté, Besançon, France.
authors: Amit
authors: A
authors: Kumar
authors: Department of Rheumatology, Centre Hospitalier Régional Universitaire, Besançon, France.
authors: Xavier
authors: X
authors: Guillot
authors: Pathogens & Inflammation Laboratory, University of Franche-Comté, Besançon, France.
authors: Kashif Aziz
authors: KA
authors: Khan
authors: Department of Rheumatology, Centre Hospitalier Régional Universitaire, Besançon, France.
authors: Claire
authors: C
authors: Vidon
authors: Pathogens & Inflammation Laboratory, University of Franche-Comté, Besançon, France.
authors: Laurie
authors: L
authors: Coquard
authors: Pathogens & Inflammation Laboratory, University of Franche-Comté, Besançon, France; Clinical Investigation Biotherapy Center506, Centre Hospitalier Régional Universitaire, Besançon, France; Department of Therapeutics, University of Franche Comté, Besançon, France.
authors: Eric
authors: E
authors: Toussirot
authors: Department of Rheumatology, Centre Hospitalier Régional Universitaire, Besançon, France.
authors: Clément
authors: C
authors: Prati
authors: Pathogens & Inflammation Laboratory, University of Franche-Comté, Besançon, France; Department of Virology, Centre Hospitalier Régional Universitaire, Besançon, France; Structure Fédérative de Recherche 4234, University of Franche-Comté, Besançon, France.
authors: Georges
authors: G
authors: Herbein
mesh_terms: D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000473:pathology*; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D053760:Interleukin-23 Subunit p19 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D056564:Sirtuin 1 / Q000097:blood*
chemical_list: D015415:Biomarkers; C508840:IL23A protein, human; D053760:Interleukin-23 Subunit p19; D015850:Interleukin-6; C447939:SIRT1 protein, human; D056564:Sirtuin 1