Monomethylfumarate reduces in vitro migration of mononuclear cells.
Neurol Sci
; 35(7): 1121-5, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24504620
ABSTRACT
Migration of immunocompetent cells into the central nervous system represents a key event in the immunopathogenesis of multiple sclerosis (MS). Fumaric acid esters have recently been approved for patients with MS. Their mode of action is not fully understood so far. We analyzed the effect of monomethylfumarate (MMF), the immediate metabolite of dimethylfumarate, on migration of lymphocytes and macrophages. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with MS and healthy donors. PBMCs were treated with MMF in vitro and their migratory capacity was studied in a Boyden chamber assay. In addition, expression of matrix metalloproteinases (MMPs), chemokine receptors, adhesion molecules, and molecules of the oxidative stress cascade was assessed. MMF decreased the migratory capacity of T lymphocytes, but not of macrophages. Lymphocytes as well as macrophages responded to MMF by the upregulation of oxidative stress molecules; however, no effect was seen on the expression of MMPs, chemokine receptors, and adhesion molecules. There was no difference in comparison with cells from healthy controls. MMF reduces the migratory activity of lymphocytes most likely by changing their activational state. This points to a potential novel mode of action differentiating this drug from other available immunotherapies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucócitos Mononucleares
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Movimento Celular
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Regulação da Expressão Gênica
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Fumaratos
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Maleatos
/
Esclerose Múltipla
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Neurol Sci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Alemanha