Brain endothelial PPARgamma 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 (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.
Klotz
Luisa
L
Institute of Molecular Medicine and Experimental Immunology, University of Bonn, Sigmund-Freud-Strasse 25, Bonn, Germany. luisa.klotz@ukb.uni-bonn.de
Diehl
Linda
L
Dani
Indra
I
Neumann
Harald
H
von Oppen
Nanette
N
Dolf
Andreas
A
Endl
Elmar
E
Klockgether
Thomas
T
Engelhardt
Britta
B
Knolle
Percy
P
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000276:immunology* / Q000503:physiopathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D002536:Cerebral Arteries / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004660:Encephalitis / Q000276:immunology* / Q000503:physiopathology; D042783:Endothelial Cells / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000077205:Pioglitazone