TY  - JOUR
A1  - Schuhmann, Michael K.
A1  - Bittner, Stefan
A1  - Meuth, Sven G.
A1  - Kleinschnitz, Christoph
A1  - Fluri, Felix
T1  - Fingolimod (FTY720-P) does not stabilize the blood-brain barrier under inflammatory conditions in an in vitro model
JF  - International Journal of Molecular Sciences
N2  - 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 (S1P\(_1\)). Fingolimod phosphate (FTY720-P) a functional S1P\(_1\) 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 permeabilityin particular, on the tight junction proteins occludin, claudin 5 and ZO-1has 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 S1P\(_1\) plays a dual role in vascular permeability, depending on its ligand. Thus, S1P\(_1\) provides a mechanistic basis for FTY720-P-associated disruption of endothelial barrierssuch as the blood-retinal barrierwhich might result in macular edema.
KW  - randomized controlled trial
KW  - Sphingosine 1-Phosphate
KW  - vascular permeability
KW  - rat brain microvascular endothelial cell culture
KW  - tight junctions
KW  - FTY720-P
KW  - blood-brain barrier
KW  - inflammation
KW  - novo renal transplantation
KW  - endothelial cells
KW  - experimental autoimmune encephalomyelitis
KW  - relapsing multiple sclerosis
KW  - Zonula Occludens-1
KW  - matrix metalloproteinases
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145047
VL  - 16
ER  -