Open Access Highly Accessed Research article

Troglitazone, a PPAR-γ activator prevents endothelial cell adhesion molecule expression and lymphocyte adhesion mediated by TNF-α

Makoto Sasaki1, Paul Jordan2, Tomas Welbourne1, Alireza Minagar3, Takashi Joh4, Makoto Itoh4, John W Elrod1 and J Steven Alexander1*

Author Affiliations

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

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BMC Physiology 2005, 5:3  doi:10.1186/1472-6793-5-3

Published: 6 February 2005

Abstract

Background

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).

Results

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.

Conclusions

These results suggest that PPAR-γ agonists like troglitazone may be useful in the clinical treatment of IBD.