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Dimethyl Fumarate Suppresses Demyelination and Axonal Loss through Reduction in Pro-Inflammatory Macrophage-Induced Reactive Astrocytes and Complement C3 Deposition
Dimethyl fumarate (DMF) is an oral agent for relapsing-remitting multiple sclerosis (RRMS). In this study, we investigated the therapeutic mechanism of DMF using experimental autoimmune encephalomyelitis (EAE). DMF treatment decreased the proliferation of T cells and the production of IL-17A and GM-...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922578/ https://www.ncbi.nlm.nih.gov/pubmed/33669652 http://dx.doi.org/10.3390/jcm10040857 |
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author | Yadav, Sudhir K. Ito, Naoko Soin, Devika Ito, Kouichi Dhib-Jalbut, Suhayl |
author_facet | Yadav, Sudhir K. Ito, Naoko Soin, Devika Ito, Kouichi Dhib-Jalbut, Suhayl |
author_sort | Yadav, Sudhir K. |
collection | PubMed |
description | Dimethyl fumarate (DMF) is an oral agent for relapsing-remitting multiple sclerosis (RRMS). In this study, we investigated the therapeutic mechanism of DMF using experimental autoimmune encephalomyelitis (EAE). DMF treatment decreased the proliferation of T cells and the production of IL-17A and GM-CSF. DMF treatment also decreased the development and/or infiltration of macrophages in the central nervous system (CNS), and reduced the ratio of iNOS(+) pro-inflammatory macrophage versus Ym1(+) immunomodulatory macrophages. Furthermore, DMF treatment suppressed the deposition of complement C3 (C3) and development of reactive C3(+) astrocytes. The decrease in iNOS(+) macrophages, C3(+)astrocytes, and C3 deposition in the CNS resulted in the reduction in demyelination and axonal loss. This study suggests that the beneficial effects of DMF involve the suppression of iNOS(+) pro-inflammatory macrophages, C3(+) astrocytes, and deposition of C3 in the CNS. |
format | Online Article Text |
id | pubmed-7922578 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79225782021-03-03 Dimethyl Fumarate Suppresses Demyelination and Axonal Loss through Reduction in Pro-Inflammatory Macrophage-Induced Reactive Astrocytes and Complement C3 Deposition Yadav, Sudhir K. Ito, Naoko Soin, Devika Ito, Kouichi Dhib-Jalbut, Suhayl J Clin Med Article Dimethyl fumarate (DMF) is an oral agent for relapsing-remitting multiple sclerosis (RRMS). In this study, we investigated the therapeutic mechanism of DMF using experimental autoimmune encephalomyelitis (EAE). DMF treatment decreased the proliferation of T cells and the production of IL-17A and GM-CSF. DMF treatment also decreased the development and/or infiltration of macrophages in the central nervous system (CNS), and reduced the ratio of iNOS(+) pro-inflammatory macrophage versus Ym1(+) immunomodulatory macrophages. Furthermore, DMF treatment suppressed the deposition of complement C3 (C3) and development of reactive C3(+) astrocytes. The decrease in iNOS(+) macrophages, C3(+)astrocytes, and C3 deposition in the CNS resulted in the reduction in demyelination and axonal loss. This study suggests that the beneficial effects of DMF involve the suppression of iNOS(+) pro-inflammatory macrophages, C3(+) astrocytes, and deposition of C3 in the CNS. MDPI 2021-02-19 /pmc/articles/PMC7922578/ /pubmed/33669652 http://dx.doi.org/10.3390/jcm10040857 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yadav, Sudhir K. Ito, Naoko Soin, Devika Ito, Kouichi Dhib-Jalbut, Suhayl Dimethyl Fumarate Suppresses Demyelination and Axonal Loss through Reduction in Pro-Inflammatory Macrophage-Induced Reactive Astrocytes and Complement C3 Deposition |
title | Dimethyl Fumarate Suppresses Demyelination and Axonal Loss through Reduction in Pro-Inflammatory Macrophage-Induced Reactive Astrocytes and Complement C3 Deposition |
title_full | Dimethyl Fumarate Suppresses Demyelination and Axonal Loss through Reduction in Pro-Inflammatory Macrophage-Induced Reactive Astrocytes and Complement C3 Deposition |
title_fullStr | Dimethyl Fumarate Suppresses Demyelination and Axonal Loss through Reduction in Pro-Inflammatory Macrophage-Induced Reactive Astrocytes and Complement C3 Deposition |
title_full_unstemmed | Dimethyl Fumarate Suppresses Demyelination and Axonal Loss through Reduction in Pro-Inflammatory Macrophage-Induced Reactive Astrocytes and Complement C3 Deposition |
title_short | Dimethyl Fumarate Suppresses Demyelination and Axonal Loss through Reduction in Pro-Inflammatory Macrophage-Induced Reactive Astrocytes and Complement C3 Deposition |
title_sort | dimethyl fumarate suppresses demyelination and axonal loss through reduction in pro-inflammatory macrophage-induced reactive astrocytes and complement c3 deposition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922578/ https://www.ncbi.nlm.nih.gov/pubmed/33669652 http://dx.doi.org/10.3390/jcm10040857 |
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