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KMID : 0620920070390010027
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Experimental & Molecular Medicine
2007 Volume.39 No. 1 p.27 ~ p.37
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Extracellular HIV-1 Tat enhances monocyte adhesion by up-regulation of ICAM-1 and VCAM-1 gene expression via ROS-dependent NF-kB activation in astrocytes
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Song Ha-Yong
Choi Soo-Young
Ryu Ji-Yoon
Ju Sung-Mi
Park Lee-Jin
Lee Ji-Ae
Park Jin-Sook
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Abstract
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One of characteristic features of AIDS-related encephalitis and dementia is the infiltration of monocytes into the CNS. HIV-1 Tat was demonstrated to facilitate monocyte entry into the CNS. In this study, we examined the effect of HIV-1 Tat on the expression of adhesion molecules, generation of reactive oxygen species (ROS) and NF-kB activation in CRT-MG human astroglioma cells. Treatment of CRT-MG cells with HIV-1 Tat protein significantly increased protein and mRNA levels of ICAM-1 and VCAM-1, as measured by Western blot analysis and RT-PCR, indicating that Tat increases these protein levels at an mRNA level. In addition, Tat induced the activation of NF-kB in astrocytes. Treatment of CRT-MG with NF-kB inhibitors led to decrease in Tat-induced protein and mRNA expression of ICAM-1 and VCAM- 1. Furthermore, HIV-1 Tat protein increased ROS generation. Inhibition of Tat-induced ROS generation by N-acetyl cysteine, vitamin C and diphenyl iodonium suppressed Tat-induced NF-kB activation, ICAM-1 and VCAM-1 expression, and monocyte adhesion in CRT-MG. These data indicate that HIV-1 Tat can modulate monocyte adhesiveness by increasing expression of adhesion molecules such as ICAM-1 and VCAM-1 via ROS- and NF-kB-dependent mechanisms in astrocytes.
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KEYWORD
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astrocytes, cell adhesion molecules, inflammation, intercellular adhesion molecule-1, NF-kB, eactive oxygen species, Tat protein HIV-1, vascularcell adhesion molecule-1
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