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.
Artículo
en Inglés
| WPRIM
| ID: wpr-103080
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.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Células Tumorales Cultivadas
/
Infecciones por VIH
/
Regulación hacia Arriba
/
Astrocitos
/
FN-kappa B
/
Complejo SIDA Demencia
/
VIH-1
/
Factor de Necrosis Tumoral alfa
/
Metaloproteinasa 9 de la Matriz
/
Quinasas de Proteína Quinasa Activadas por Mitógenos
Límite:
Humanos
Idioma:
Inglés
Revista:
Experimental & Molecular Medicine
Año:
2009
Tipo del documento:
Artículo
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