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Fingolimod promotes blood–nerve barrier properties in vitro
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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893339/ https://www.ncbi.nlm.nih.gov/pubmed/29670818 http://dx.doi.org/10.1002/brb3.924 |
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author | Nishihara, Hideaki Maeda, Toshihiko Sano, Yasuteru Ueno, Maho Okamoto, Nana Takeshita, Yukio Shimizu, Fumitaka Koga, Michiaki Kanda, Takashi |
author_facet | Nishihara, Hideaki Maeda, Toshihiko Sano, Yasuteru Ueno, Maho Okamoto, Nana Takeshita, Yukio Shimizu, Fumitaka Koga, Michiaki Kanda, Takashi |
author_sort | Nishihara, Hideaki |
collection | PubMed |
description | 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 (HPnMEC) was used to evaluate BNB barrier properties. We examined tight junction proteins and barrier functions of HPnMECs 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 HPnMECs. Conversely, typical CIDP sera decreased claudin‐5 mRNA/protein levels and TEER values in HPnMECs; 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. |
format | Online Article Text |
id | pubmed-5893339 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58933392018-04-18 Fingolimod promotes blood–nerve barrier properties in vitro Nishihara, Hideaki Maeda, Toshihiko Sano, Yasuteru Ueno, Maho Okamoto, Nana Takeshita, Yukio Shimizu, Fumitaka Koga, Michiaki Kanda, Takashi Brain Behav Original Research 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 (HPnMEC) was used to evaluate BNB barrier properties. We examined tight junction proteins and barrier functions of HPnMECs 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 HPnMECs. Conversely, typical CIDP sera decreased claudin‐5 mRNA/protein levels and TEER values in HPnMECs; 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. John Wiley and Sons Inc. 2018-03-25 /pmc/articles/PMC5893339/ /pubmed/29670818 http://dx.doi.org/10.1002/brb3.924 Text en © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Nishihara, Hideaki Maeda, Toshihiko Sano, Yasuteru Ueno, Maho Okamoto, Nana Takeshita, Yukio Shimizu, Fumitaka Koga, Michiaki Kanda, Takashi Fingolimod promotes blood–nerve barrier properties in vitro |
title | Fingolimod promotes blood–nerve barrier properties in vitro |
title_full | Fingolimod promotes blood–nerve barrier properties in vitro |
title_fullStr | Fingolimod promotes blood–nerve barrier properties in vitro |
title_full_unstemmed | Fingolimod promotes blood–nerve barrier properties in vitro |
title_short | Fingolimod promotes blood–nerve barrier properties in vitro |
title_sort | fingolimod promotes blood–nerve barrier properties in vitro |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893339/ https://www.ncbi.nlm.nih.gov/pubmed/29670818 http://dx.doi.org/10.1002/brb3.924 |
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