Interferon-beta stabilizes barrier characteristics of brain endothelial cells in vitro.
Ann Neurol
; 56(2): 192-205, 2004 Aug.
Article
em En
| MEDLINE
| ID: mdl-15293271
ABSTRACT
Multiple sclerosis (MS) is accompanied by a breakdown of the blood-brain barrier (BBB) leading to edema formation and aggravation of the disease. Interferon-beta (IFN-beta) has been approved for the treatment of MS and besides its immunomodulatory effects has been demonstrated to lead to a stabilization of BBB integrity in vivo. To investigate whether human recombinant IFN-beta exerts direct effects on the BBB, we used an in vitro BBB model in which brain endothelial cells in coculture with astrocytes form a tight permeability barrier for 3H-inulin and 14C-sucrose. Removal of the astrocytes from the coculture or alternatively addition of histamine resulted in an increased paracellular permeability for small tracers across the brain endothelial cell monolayer. Strikingly, in the presence of IFN-beta, permeability increase under both conditions was inhibited. Permeability changes were accompanied by minor changes in the staining for tight junction-associated proteins in brain endothelial cell monolayers. Taken together, our data demonstrate a direct stabilizing effect of IFN-beta on BBB cerebral endothelial cells in vitro that might significantly contribute to the beneficial effects of IFN-beta treatment in MS in vivo.
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Bases de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Interferon beta
/
Células Endoteliais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Ann Neurol
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Alemanha