title: Troglitazone, a PPAR-gamma activator prevents endothelial cell adhesion molecule expression and lymphocyte adhesion mediated by TNF-alpha.
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-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.
authors.affiliation: Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, LA 71130, USA. makoto@dpc.aichi-gakuin.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Sasaki
authors.forename: Paul
authors.initials: P
authors.lastname: Jordan
authors.forename: Tomas
authors.initials: T
authors.lastname: Welbourne
authors.forename: Alireza
authors.initials: A
authors.lastname: Minagar
authors.forename: Takashi
authors.initials: T
authors.lastname: Joh
authors.forename: Makoto
authors.initials: M
authors.lastname: Itoh
authors.forename: John W
authors.initials: JW
authors.lastname: Elrod
authors.forename: J Steven
authors.initials: JS
authors.lastname: Alexander
mesh_terms: 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
chemical_list: 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