Fingolimod FTY720-P Does Not Stabilize the Blood–Brain Barrier under Inflammatory Conditions in an in Vitro ModelReportar como inadecuado




Fingolimod FTY720-P Does Not Stabilize the Blood–Brain Barrier under Inflammatory Conditions in an in Vitro Model - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

1

Department of Neurology, University of Würzburg, Würzburg 97080, Germany

2

Department of Neurology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz 55131, Germany

3

Department of Neurology, University of Münster, Münster 48149, Germany

4

Department of Physiology I-Neuropathophysiology, University of Münster, Münster 48149, Germany





*

Author to whom correspondence should be addressed.



Academic Editor: Katalin Prokai-Tatrai

Abstract Breakdown of the blood-brain barrier BBB is an early hallmark of multiple sclerosis MS, a progressive inflammatory disease of the central nervous system. Cell adhesion in the BBB is modulated by sphingosine-1-phosphate S1P, a signaling protein, via S1P receptors S1P1. Fingolimod phosphate FTY720-P a functional S1P1 antagonist has been shown to improve the relapse rate in relapsing-remitting MS by preventing the egress of lymphocytes from lymph nodes. However, its role in modulating BBB permeability—in particular, on the tight junction proteins occludin, claudin 5 and ZO-1—has not been well elucidated to date. In the present study, FTY720-P did not change the transendothelial electrical resistance in a rat brain microvascular endothelial cell RBMEC culture exposed to inflammatory conditions and thus did not decrease endothelial barrier permeability. In contrast, occludin was reduced in RBMEC culture after adding FTY720-P. Additionally, FTY720-P did not alter the amount of endothelial matrix metalloproteinase MMP-9 and MMP-2 in RBMEC cultures. Taken together, our observations support the assumption that S1P1 plays a dual role in vascular permeability, depending on its ligand. Thus, S1P1 provides a mechanistic basis for FTY720-P-associated disruption of endothelial barriers—such as the blood-retinal barrier—which might result in macular edema. View Full-Text

Keywords: FTY720-P; blood-brain barrier; rat brain microvascular endothelial cell culture; inflammation; tight junctions FTY720-P; blood-brain barrier; rat brain microvascular endothelial cell culture; inflammation; tight junctions





Autor: Michael K. Schuhmann 1, Stefan Bittner 2, Sven G. Meuth 3,4, Christoph Kleinschnitz 1 and Felix Fluri 1,*

Fuente: http://mdpi.com/



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