Ciglitazone, a peroxisome proliferator-activated receptor gamma ligand, inhibits proliferation and differentiation of th17 cells

• Published in: Biomolecules & therapeutics Vol. 23; no. 1; pp. 71 - 76
• Main Authors: Kim, Dong Hyeok, Ihn, Hyun-Ju, Moon, Chaerin, Oh, Sang-Seok, Park, Soojong, Kim, Suk, Lee, Keun Woo, Kim, Kwang Dong
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Society of Applied Pharmacology 01.01.2015; 한국응용약물학회
• Subjects: Original; 약학; Cell proliferation; CCNB1; Th17 cell; PPARγ; IL-17
• ISSN: 1976-9148; 2005-4483; 1976-9148; 2005-4483
• DOI: 10.4062/biomolther.2014.042

Peroxisome proliferator-activated receptor gamma (PPARγ) 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 PPARγ-mediated inhibition of Th17 cell differentiation and cytokine production at an early stage. Treatment with ciglitazone, a PPARγ ligand, reduced both IL-1β-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-1β. 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 PPARγ activator might be a potent candidate for treatment of Th17-mediated autoimmune disease patients.