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:

17 Mar 2015 22:02

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)

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