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Dysregulated serum IL-23 and SIRT1 activity in peripheral blood mononuclear cells of patients with rheumatoid arthritis.
PLoS One. 2015; 10(3):e0119981.Plos

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+Show Affiliations

Department of Rheumatology, Centre Hospitalier Régional Universitaire, Besançon, France; Pathogens & Inflammation Laboratory, University of Franche-Comté, Besançon, France.Pathogens & Inflammation Laboratory, University of Franche-Comté, Besançon, France.Department of Rheumatology, Centre Hospitalier Régional Universitaire, Besançon, France.Pathogens & Inflammation Laboratory, University of Franche-Comté, Besançon, France.Department of Rheumatology, Centre Hospitalier Régional Universitaire, Besançon, France.Pathogens & Inflammation Laboratory, University of Franche-Comté, Besançon, France.Department of Rheumatology, Centre Hospitalier Régional Universitaire, Besançon, France.Pathogens & Inflammation Laboratory, University of Franche-Comté, Besançon, France.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.Department of Rheumatology, Centre Hospitalier Régional Universitaire, Besançon, France.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.

Pub Type(s)

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

Language

eng

PubMed ID

25799392

Citation

Wendling, Daniel, et al. "Dysregulated Serum IL-23 and SIRT1 Activity in Peripheral Blood Mononuclear Cells of Patients With Rheumatoid Arthritis." PloS One, vol. 10, no. 3, 2015, pp. e0119981.
Wendling D, Abbas W, Godfrin-Valnet M, et al. Dysregulated serum IL-23 and SIRT1 activity in peripheral blood mononuclear cells of patients with rheumatoid arthritis. PLoS ONE. 2015;10(3):e0119981.
Wendling, D., Abbas, W., Godfrin-Valnet, M., Kumar, A., Guillot, X., Khan, K. A., Vidon, C., Coquard, L., Toussirot, E., Prati, C., & Herbein, G. (2015). Dysregulated serum IL-23 and SIRT1 activity in peripheral blood mononuclear cells of patients with rheumatoid arthritis. PloS One, 10(3), e0119981. https://doi.org/10.1371/journal.pone.0119981
Wendling D, et al. Dysregulated Serum IL-23 and SIRT1 Activity in Peripheral Blood Mononuclear Cells of Patients With Rheumatoid Arthritis. PLoS ONE. 2015;10(3):e0119981. PubMed PMID: 25799392.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dysregulated serum IL-23 and SIRT1 activity in peripheral blood mononuclear cells of patients with rheumatoid arthritis. AU - Wendling,Daniel, AU - Abbas,Wasim, AU - Godfrin-Valnet,Marie, AU - Kumar,Amit, AU - Guillot,Xavier, AU - Khan,Kashif Aziz, AU - Vidon,Claire, AU - Coquard,Laurie, AU - Toussirot,Eric, AU - Prati,Clément, AU - Herbein,Georges, Y1 - 2015/03/23/ PY - 2014/06/26/received PY - 2015/01/16/accepted PY - 2015/3/24/entrez PY - 2015/3/24/pubmed PY - 2016/3/5/medline SP - e0119981 EP - e0119981 JF - PloS one JO - PLoS ONE VL - 10 IS - 3 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/25799392/Dysregulated_serum_IL_23_and_SIRT1_activity_in_peripheral_blood_mononuclear_cells_of_patients_with_rheumatoid_arthritis_ L2 - http://dx.plos.org/10.1371/journal.pone.0119981 DB - PRIME DP - Unbound Medicine ER -