Brain endothelial PPAR-γ controls inflammation-induced CD4+ T cell adhesion and transmigration in vitro

An important step in the pathogenesis of multiple sclerosis is adhesion and transmigration of encephalitogenic T cells across brain endothelial cells (EC) which strongly relies on interaction with EC-expressed adhesion molecules. We provide molecular evidence that the transcription factor peroxisome proliferator-activated receptor gamma (PPAR gamma) is a negative regulator of brain EC inflammation. The PPAR gamma agonist pioglitazone reduces transendothelial migration of encephalitogenic T cells across TNF alpha-stimulated brain EC. This effect is clearly PPAR gamma mediated, as lentiviral PPAR gamma overexpression in brain EC results in selective abrogation of inflammation-induced ICAM-1 and VCAM-1 upregulation and subsequent adhesion and transmigration of T cells. We therefore propose that PPAR gamma in brain EC may be exploited to target detrimental EC-T cell interactions under inflammatory conditions. (C) 2007 Elsevier B.V. All rights reserved.