Exp Mol Med.  2009 Feb;41(2):86-93. 10.3858/emm.2009.41.2.011.

Extracellular HIV-1 Tat up-regulates expression of matrix metalloproteinase-9 via a MAPK-NF-kappaB dependent pathway in human astrocytes

• Ju SM
• Song HY
• Lee JA
• Lee SJ
• Choi SY
• Park J

• KMID: 1109431
• DOI: http://doi.org/10.3858/emm.2009.41.2.011

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.

Keyword

astrocytes; gene products, tat; HIV; inflammation; matrix metalloproteinase 9; mitogen-activated protein kinases; NF-kappaB; tumor necrosis factor-alpha

MeSH Terms

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