Extracellular HIV-1 Tat up-regulates expression of matrix metalloproteinase-9 via a MAPK-NF-kappaB dependent pathway in human astrocytes.
10.3858/emm.2009.41.2.011
- Author:
Sung Mi JU
1
;
Ha Yong SONG
;
Ji Ae LEE
;
Su Jin LEE
;
Soo Young CHOI
;
Jinseu PARK
Author Information
1. Department of Biomedical Science, College of Natural Sciences, Hallym University, Chuncheon 200-702, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
astrocytes;
gene products, tat;
HIV;
inflammation;
matrix metalloproteinase 9;
mitogen-activated protein kinases;
NF-kappaB;
tumor necrosis factor-alpha
- MeSH:
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
- From:Experimental & Molecular Medicine
2009;41(2):86-93
- CountryRepublic of Korea
- Language:English
-
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.
