Ciglitazone, a Peroxisome Proliferator-Activated Receptor Gamma Ligand, Inhibits Proliferation and Differentiation of Th17 Cells.
10.4062/biomolther.2014.042
- Author:
Dong Hyeok KIM
1
;
Hyun Ju IHN
;
Chaerin MOON
;
Sang Seok OH
;
Soojong PARK
;
Suk KIM
;
Keun Woo LEE
;
Kwang Dong KIM
Author Information
1. Division of Applied Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea. kdkim88@gnu.ac.kr
- Publication Type:Original Article
- Keywords:
Th17 cell;
IL-17;
PPARgamma;
CCNB1;
Cell proliferation
- MeSH:
Arthritis, Experimental;
Autoimmune Diseases;
Cell Cycle;
Cell Proliferation;
Cytokines;
Encephalomyelitis, Autoimmune, Experimental;
Humans;
Inflammatory Bowel Diseases;
Interleukin-17;
PPAR gamma*;
T-Lymphocytes;
Th17 Cells*
- From:Biomolecules & Therapeutics
2015;23(1):71-76
- CountryRepublic of Korea
- Language:English
-
Abstract:
Peroxisome proliferator-activated receptor gamma (PPARgamma) was identified as a cell-intrinsic regulator of Th17 cell differentiation. Th17 cells have been associated with several autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), inflammatory bowel disease (IBD), and collagen-induced arthritis. In this study, we confirmed PPARgamma-mediated inhibition of Th17 cell differentiation and cytokine production at an early stage. Treatment with ciglitazone, a PPARgamma ligand, reduced both IL-1beta-mediated enhancement of Th17 differentiation and activation of Th17 cells after polarization. For Th17 cell differentiation, we found that ciglitazone-treated cells had a relatively low proliferative activity and produced a lower amount of cytokines, regardless of the presence of IL-1beta. The inhibitory activity of ciglitazone might be due to decrease of CCNB1 expression, which regulates the cell cycle in T cells. Hence, we postulate that a pharmaceutical PPARgamma activator might be a potent candidate for treatment of Th17-mediated autoimmune disease patients.
