Abstract
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 (PPARγ) is a negative regulator of brain EC inflammation. The PPARγ agonist pioglitazone reduces transendothelial migration of encephalitogenic T cells across TNFα-stimulated brain EC. This effect is clearly PPARγ mediated, as lentiviral PPARγ 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 PPARγ in brain EC may be exploited to target detrimental EC-T cell interactions under inflammatory conditions.
Original language | English |
---|---|
Pages (from-to) | 34-43 |
Number of pages | 10 |
Journal | Journal of Neuroimmunology |
Volume | 190 |
Issue number | 1-2 |
DOIs | |
State | Published - Oct 2007 |
Externally published | Yes |
Keywords
- Adhesion
- Endothelial cells
- Transcription factor
- Transmigration