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Sasaki, M. et al.

Sasaki, Jordan, Welbourne, Minagar, Joh, Itoh, Elrod, Alexander,

Troglitazone, a PPAR-gamma activator prevents endothelial cell adhesion molecule expression and lymphocyte adhesion mediated by TNF-alpha.

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-gamma (PPAR-gamma), 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 microM), significantly reduced the TNF-alpha (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 (20 microM) reduced TNF-alpha induced VCAM-1, ICAM-1 and E-selectin expression. Moreover, troglitazone significantly reduced alpha4beta7-integrin dependent lymphocyte adhesion to TNF-alpha cultured endothelial cells. CONCLUSIONS: These results suggest that PPAR-gamma agonists like troglitazone may be useful in the clinical treatment of IBD.[1]

References

Troglitazone, a PPAR-gamma activator prevents endothelial cell adhesion molecule expression and lymphocyte adhesion mediated by TNF-alpha. Sasaki, M., Jordan, P., Welbourne, T., Minagar, A., Joh, T., Itoh, M., Elrod, J.W., Alexander, J.S. BMC Physiol. (2005) [Pubmed]

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