Biomol Ther.  2015 Jan;23(1):71-76. 10.4062/biomolther.2014.042.

Ciglitazone, a Peroxisome Proliferator-Activated Receptor Gamma Ligand, Inhibits Proliferation and Differentiation of Th17 Cells

• Kim DH
• Ihn HJ
• Moon C
• Oh SS
• Park S
• Kim S
• Lee KW
• Kim KD

• KMID: 2380365
• DOI: http://doi.org/10.4062/biomolther.2014.042

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.

Keyword

Th17 cell; IL-17; PPARgamma; CCNB1; Cell proliferation

MeSH Terms

Arthritis, Experimental
Autoimmune Diseases
Cell Cycle
Cell Proliferation
Cytokines
Encephalomyelitis, Autoimmune, Experimental
Humans
Inflammatory Bowel Diseases
Interleukin-17
PPAR gamma*
T-Lymphocytes
Th17 Cells*
Cytokines
Interleukin-17
PPAR gamma