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

• Published in: Experimental & molecular medicine Vol. 39; no. 1; pp. 27 - 37
• Main Authors: Song, Ha Yong, Ryu, Jiyoon, Ju, Sung Mi, Park, Lee Jin, Lee, Ji Ae, Choi, Soo Young, Park, Jinseu
• Format: Journal Article
• Language: English
• Published: 28.02.2007
• Subjects: Lentivirus
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/emm.2007.4

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