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

Klotz, Luisa; Diehl, Linda; Dani, Indra; Neumann, Harald; von Oppen, Nanette; Dolf, Andreas; Endl, Elmar; Klockgether, Thomas; Engelhardt, Britta; Knolle, Percy (2007). Brain endothelial PPARgamma controls inflammation-induced CD4+ T cell adhesion and transmigration in vitro. Journal of neuroimmunology, 190(1-2), pp. 34-43. Amsterdam: Elsevier 10.1016/j.jneuroim.2007.07.017

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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 (PPARgamma) is a negative regulator of brain EC inflammation. The PPARgamma agonist pioglitazone reduces transendothelial migration of encephalitogenic T cells across TNFalpha-stimulated brain EC. This effect is clearly PPARgamma mediated, as lentiviral PPARgamma 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 PPARgamma in brain EC may be exploited to target detrimental EC-T cell interactions under inflammatory conditions.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
UniBE Contributor:	Engelhardt, Britta
ISSN:	0165-5728
ISBN:	17719655
Publisher:	Elsevier
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:55
Last Modified:	05 Dec 2022 14:17
Publisher DOI:	10.1016/j.jneuroim.2007.07.017
PubMed ID:	17719655
Web of Science ID:	000251186000007
URI:	https://boris.unibe.ch/id/eprint/23654 (FactScience: 43301)