Dimethyl Fumarate Suppresses Demyelination and Axonal Loss through Reduction in Pro-Inflammatory Macrophage-Induced Reactive Astrocytes and Complement C3 Deposition.
J Clin Med
; 10(4)2021 Feb 19.
Article
em En
| MEDLINE
| ID: mdl-33669652
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
J Clin Med
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos