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.
Sasaki
Makoto
M
Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, LA 71130, USA. makoto@dpc.aichi-gakuin.ac.jp
Jordan
Paul
P
Welbourne
Tomas
T
Minagar
Alireza
A
Joh
Takashi
T
Itoh
Makoto
M
Elrod
John W
JW
Alexander
J Steven
JS
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008024:Ligands; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D009088:Mucoproteins; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015815:Cell Adhesion Molecules; D002839:Chromans; D019040:E-Selectin; D008024:Ligands; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000077288:Troglitazone