Extracellular HIV-1 Tat up-regulates expression of matrix metalloproteinase-9 via a MAPK-NF-kappaB dependent pathway in human astrocytes
Experimental & Molecular Medicine
; : 86-93, 2009.
Article
em En
| WPRIM
| ID: wpr-103080
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WPRO
ABSTRACT
The infiltration of monocytes into the CNS represents one of the early steps to inflammatory events in AIDS-related encephalitis and dementia. Increased activity of selected matrix metalloproteinases (MMPs) such as MMP-9 impairs the integrity of blood-brain barrier leading to enhanced monocyte infiltration into the CNS. In this study, we examined the effect of HIV-1 Tat on the expression of MMP-9 in CRT-MG human astroglioma cells. Treatment of CRT-MG cells with HIV-1 Tat protein significantly increased protein levels of MMP-9, as measured by Western blot analysis, zymography and an ELISA. Treatment of CRT-MG cells with HIV-1 Tat protein markedly increased mRNA levels of MMP-9, as analyzed by RT-PCR. Pretreatment of CRT-MG cells with NF-kappaB inhibitors led to decrease in Tat-induced protein and mRNA expression of MMP-9. Pretreatment of CRT-MG cells with MAPK inhibitors suppressed Tat-induced MMP-9 expression. Furthermore, HIV-1 Tat-induced expression of MMP-9 was significantly inhibited by neutralization of TNF-alpha, but not IL-1beta and IL-6. Taken together, our results indicate that HIV-1 Tat can up-regulate expression of MMP-9 via MAPK-NF-kappaB-dependent mechanisms as well as Tat-induced TNF-alpha production in astrocytes.
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Base de dados:
WPRIM
Assunto principal:
Células Tumorais Cultivadas
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Infecções por HIV
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Regulação para Cima
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Astrócitos
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NF-kappa B
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Complexo AIDS Demência
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HIV-1
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Fator de Necrose Tumoral alfa
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Metaloproteinase 9 da Matriz
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Quinases de Proteína Quinase Ativadas por Mitógeno
Limite:
Humans
Idioma:
En
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2009
Tipo de documento:
Article