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KMID : 0620920090410020086
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Experimental & Molecular Medicine
2009 Volume.41 No. 2 p.86 ~ p.93
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Extracellular HIV-1 Tat up-regulates expression of matrix metalloproteinase-9 via a MAPK-NF-κB dependent pathway in human astrocytes
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Ju Sung-Mi
Choi Soo-Young
Park Jin-Sook
Song Ha-Yong
Lee Ji-Ae
Lee Su-Jin
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Abstract
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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-κB 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-α, but not IL-1β and IL-6. Taken together, our results indicate that HIV-1 Tat can up-regulate expression of MMP-9 via MAPK-NF-κB-dependent mechanisms as well as Tat-induced TNF-α production in astrocytes.
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KEYWORD
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astrocytes, gene products, tat, HIV, inflammation, matrix metalloproteinase 9, mitogenactivated protein kinases, NF-κB, tumor necrosis factor-α
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