Impact of glucocorticoids on systemic sirtuin 1 expression and activity in rats with adjuvant-induced arthritis.
Fiche publication
Date publication
juillet 2020
Journal
Epigenetics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr HERBEIN Georges
Tous les auteurs :
Pasquereau S, Totoson P, Nehme Z, Abbas W, Kumar A, Verhoeven F, Prati C, Wendling D, Demougeot C, Herbein G
Lien Pubmed
Résumé
The class III histone deacetylase sirtuin 1 (SIRT1) plays a pivotal role in numerous biological and physiological functions throughout lifespan, including inflammation. A possible association between SIRT1 and proinflammatory cytokines might exist. In addition to their important role in endorsing inflammation, articular destruction, and comorbidities associated with rheumatoid arthritis (RA), pro-inflammatory cytokines mediates the development of systemic effects such as anemia, cardiovascular diseases, fatigue and depression. Here, we aimed to evaluate systemic SIRT1 expression and enzymatic activity using western blotting and colorimetric assay respectively, in peripheral blood mononuclear cells (PBMCs) and in liver isolated from rats with adjuvant-induced arthritis (AIA), treated or not with low or high doses of glucocorticoids (GCs). We also measured the production of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF) and interleukin-1 beta (IL-1 beta) in PBMCs and liver of those rats using an ELISA assay. We found that SIRT1 expression and activity are increased in PBMCs of AIA rats compared to healthy controls and decreased under GC treatment. Similarly, we observed an increased SIRT1 activity in the liver of AIA rats compared to healthy controls which decreased under high doses of GCs. We also found an increase in levels of IL-1 beta and TNF in the liver of rats with AIA compared to healthy controls, which were subsequently decreased under high doses of GC. Independently of the tissue studied (PBMCs, liver), we did not observe a significant correlation between SIRT1 activity and proinflammatory cytokine production. In contrast, a strong positive correlation was found between the liver levels of TNF and IL-1 beta (rho=0.9503, p= 7.5x10). Our results indicate that increased inflammation in AIA rats compared to healthy control is accompanied by an increased SIRT1 activity in both PBMCs and liver, which could be decreased under GC treatment.
Mots clés
AIA, IL-1 beta, PBMCs, SIRT1, Sirtuin 1, TNF alpha, adjuvant-induced arthritis, liver
Référence
Epigenetics. 2020 Jul 2;: