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Experimental & Molecular Medicine ; : 86-93, 2009.
Article in English | 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.


Subject(s)
Humans , AIDS Dementia Complex/metabolism , Astrocytes/drug effects , HIV Infections/complications , HIV-1 , Matrix Metalloproteinase 9/genetics , Mitogen-Activated Protein Kinase Kinases/metabolism , NF-kappa B/metabolism , Tumor Cells, Cultured , Tumor Necrosis Factor-alpha/immunology , Up-Regulation/drug effects , tat Gene Products, Human Immunodeficiency Virus/metabolism
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