Troglitazone, a PPAR-γ activator prevents endothelial cell adhesion molecule expression and lymphocyte adhesion mediated by TNF-α
1 Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, LA, 71130, USA
2 Department of Gastroenterology, LSU Health Sciences Center, Shreveport, LA, 71130, USA
3 Department of Neurology, LSU Health Sciences Center, Shreveport, LA, USA, 71130, USA
4 Nagoya City University Graduate School of Medical Sciences, Departments of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi-Mizuho, Nagoya 467-8601, Japan
BMC Physiology 2005, 5:3 doi:10.1186/1472-6793-5-3Published: 6 February 2005
Cytokine mediated induction of the mucosal addressin cell adhesion molecule-1(MAdCAM-1) expression is associated with the onset and progression of inflammatory bowel disease (IBD).
Using western blotting and cell-based ELISA, we show in this study that troglitazone, an activator of the peroxisome proliferator-activated receptor-γ (PPAR-γ), widely used in the treatment of diabetes, has as well recently been highlighted as protective in models of inflammation and cancer. We found that troglitazone (10–40 μM), significantly reduced the TNF-α (1 ng/ml) mediated induction of endothelial MAdCAM-1 in a dose-dependent manner, achieving a 34.7% to 98.4% reduction in induced MAdCAM-1. Trogliazone (20μM) reduced TNF-α induced VCAM-1, ICAM-1 and E-selectin expression. Moreover, troglitazone significantly reduced α4β7-integrin dependent lymphocyte adhesion to TNF-α cultured endothelial cells.
These results suggest that PPAR-γ agonists like troglitazone may be useful in the clinical treatment of IBD.