Open AccessFingolimod promotes blood–nerve barrier properties in vitro
Author(s) -
Nishihara Hideaki,
Maeda Toshihiko,
Sano Yasuteru,
Ueno Maho,
Okamoto Nana,
Takeshita Yukio,
Shimizu Fumitaka,
Koga Michiaki,
Kanda Takashi
Publication year - 2018
Publication title -
brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.915
H-Index - 41
ISSN - 2162-3279
DOI - 10.1002/brb3.924
Subject(s) - fingolimod , blood–brain barrier , chronic inflammatory demyelinating polyneuropathy , medicine , pharmacology , multiple sclerosis , immunology , chemistry , central nervous system , antibody
Objective The main effect of fingolimod is thought to be functional antagonism of lymphocytic S1P1 receptors and the prevention of lymphocyte egress from lymphoid tissues, thereby reducing lymphocyte infiltration into the nervous system. However, a growing number of reports suggest that fingolimod also has a direct effect on several cell types in the nervous system. Although we previously reported that fingolimod enhances blood–brain barrier ( BBB ) functions, there have been no investigations regarding the blood–nerve barrier ( BNB ). In this study, we examine how fingolimod affects the BNB . Methods An immortalized human peripheral nerve microvascular endothelial cell line ( HP n MEC ) was used to evaluate BNB barrier properties. We examined tight junction proteins and barrier functions of HP n MEC s in conditioned medium with or without fingolimod‐phosphate and blood sera from patients with typical chronic inflammatory demyelinating polyneuropathy ( CIDP ). Results Incubation with fingolimod‐phosphate increased levels of claudin‐5 mRNA and protein as well as TEER values in HP n MEC s. Conversely, typical CIDP sera decreased claudin‐5 mRNA /protein levels and TEER values in HP n MEC s; however, pretreatment with fingolimod‐phosphate inhibited the effects of the typical CIDP sera. Conclusions Fingolimod‐phosphate directly modifies the BNB and enhances barrier properties. This mechanism may be a viable therapeutic target for CIDP , and fingolimod may be useful in patients with typical CIDP who have severe barrier disruption.