Cytokine effects on glutamate uptake by human astrocytes.
Neuroimmunomodulation
; 7(3): 153-9, 2000.
Article
em En
| MEDLINE
| ID: mdl-10754403
ABSTRACT
Glutamate uptake by astrocytes has been postulated to play a neuroprotective role during brain inflammation. Using primary human fetal astrocyte cultures, we investigated the influence of selected cytokines on glutamate uptake activity. Interleukin (IL)-1beta and tumor necrosis factor-alpha dose-dependently inhibited astrocyte glutamate uptake, whereas interferon (IFN)-gamma alone stimulated this activity. The nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine, blocked IL-1beta-mediated inhibition of glutamate uptake, suggesting involvement of nitric oxide in the effect of IL-1beta. IL-1 receptor antagonist protein totally reversed the inhibitory effect of cytokines, suggesting a critical role of IL-1beta. The anti-inflammatory cytokine IFN-beta blocked cytokine (IL-1beta plus IFN-gamma)-induced inhibition of glutamate uptake with a corresponding reduction in nitric oxide generation. Taken together, these findings suggest that proinflammatory cytokines inhibit astrocyte glutamate uptake by a mechanism involving nitric oxide, and that IFN-beta may exert a therapeutically beneficial effect by blocking cytokine-induced nitric oxide production in inflammatory diseases of the brain.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Sialoglicoproteínas
/
Astrócitos
/
Interferon gama
/
Interleucina-1
/
Fator de Necrose Tumoral alfa
/
Interferon beta
/
Ácido Glutâmico
Limite:
Humans
Idioma:
En
Revista:
Neuroimmunomodulation
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
NEUROLOGIA
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos