Dysregulated serum IL-23 and SIRT1 activity in peripheral blood mononuclear cells of patients with rheumatoid arthritis

PLoS One. 2015 Mar 23;10(3):e0119981. doi: 10.1371/journal.pone.0119981. eCollection 2015.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / pathology*
  • 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*

Substances

  • Biomarkers
  • IL23A protein, human
  • Interleukin-23 Subunit p19
  • Interleukin-6
  • SIRT1 protein, human
  • Sirtuin 1

Grants and funding

This work was supported by grants from the University of Franche-Comté (UFC) and the Groupe de Recherche en Virologie de Franche-Comté and Europe (FEDER, Fonds Européens de Développement Régional N°2014-0045) to Georges Herbein, and by the Association Franc-Comtoise pour la Formation, la Recherche et l’Enseignement en Rhumatologie to Daniel Wendling. Amit Kumar is a recipient of a postdoctoral fellowship of the Région Franche-Comté (N° 2012C-06102). Wasim Abbas and Kashif A. Khan are recipients of doctoral scholarships from the Higher Education Commission, Pakistan. Laurie Coquard is an assistant engineer in FEDER project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.