Exp Mol Med.  2007 Feb;39(1):27-37.

Extracellular HIV-1 Tat enhances monocyte adhesion by up-regulation of ICAM-1 and VCAM-1 gene expression via ROS-dependent NF-kappaB activation in astrocytes

• Song HY
• Ryu J
• Ju SM
• Park LJ
• Lee JA
• Choi SY
• Park J

Abstract

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-kappaB 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-kappaB in astrocytes. Treatment of CRT-MG with NF-kappaB 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-kappaB 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-kappaB-dependent mechanisms in astrocytes.

Keyword

astrocytes; cell adhesion molecules; inflammation; intercellular adhesion molecule-1; NF-kappaB; reactive oxygen species; Tat protein, HIV-1; vascular cell adhesion molecule-1

MeSH Terms

Vascular Cell Adhesion Molecule-1/genetics/*metabolism
Up-Regulation/*drug effects
Transcription, Genetic/genetics
Reactive Oxygen Species/*metabolism
NF-kappa B/*metabolism
Monocytes/cytology/*drug effects/metabolism
Intercellular Adhesion Molecule-1/genetics/*metabolism
Humans
*HIV-1
Gene Products, tat/*pharmacology
Cell Line
Cell Adhesion/drug effects
Astrocytes/cytology/metabolism