Fingolimod prevents blood-brain barrier disruption induced by the sera from patients with multiple sclerosis

PloS One
Hideaki NishiharaTakashi Kanda

Abstract

Effect of fingolimod in multiple sclerosis (MS) is thought to involve the prevention of lymphocyte egress from lymphoid tissues, thereby reducing autoaggressive lymphocyte infiltration into the central nervous system across blood-brain barrier (BBB). However, brain microvascular endothelial cells (BMECs) represent a possible additional target for fingolimod in MS patients by directly repairing the function of BBB, as S1P receptors are also expressed by BMECs. In this study, we evaluated the effects of fingolimod on BMECs and clarified whether fingolimod-phosphate restores the BBB function after exposure to MS sera. Changes in tight junction proteins, adhesion molecules and transendothelial electrical resistance (TEER) in BMECs were evaluated following incubation in conditioned medium with or without fingolimod/fingolimod-phosphate. In addition, the effects of sera derived from MS patients, including those in the relapse phase of relapse-remitting (RR) MS, stable phase of RRMS and secondary progressive MS (SPMS), on the function of BBB in the presence of fingolimod-phosphate were assessed. Incubation with fingolimod-phosphate increased the claudin-5 protein levels and TEER values in BMECs, although it did not change the amount o...Continue Reading

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Citations

Dec 23, 2015·International Journal of Molecular Sciences·Michael K SchuhmannFelix Fluri
Aug 12, 2015·Seminars in Immunopathology·Luke M HealyJack P Antel
Dec 17, 2016·International Journal of Molecular Sciences·Refik PulThomas Skripuletz
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Jul 18, 2019·Neuromolecular Medicine·Efthalia Angelopoulou, Christina Piperi
Feb 20, 2020·Expert Opinion on Therapeutic Targets·Lukmanee TradtrantipAlan S Verkman
Apr 3, 2019·Immunological Medicine·Fumitaka ShimizuTakashi Kanda
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Apr 20, 2018·Brain and Behavior·Hideaki NishiharaTakashi Kanda
Dec 12, 2018·International Immunopharmacology·Shuangwen YuKaili Hu
Apr 21, 2020·Current Neuropharmacology·Yam Nath PaudelMohd Farooq Shaikh
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