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One of characteristic features of AIDS-related ence-phalitis and deme ntia is the infiltration of monocytes into the CNS. HIV-1 Tat was demonstrated to facilitate monocyte entry into the examined the effect of HIV-1 Tat on the expression of adhesion molecules, genera tion of reactive oxygen species (ROS) and NF-κB 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 mea-sured by Western blot analysis and RT-PCR, in-dicating that Tat increases these protein levels at an mRNA level. In addition, Tat induced the activation of NF-κB in astrocytes. Treatment of CRT-MG with NF-κB 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 genera-N-acetyl cysteine, vitamin C and diphenyl iodonium suppressed Tat-induced NF-κB 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 in-creasing expression of adhesion molecules such as ICAM-1 and VCAM-1 via ROS- and NF-κB-dependent mechanisms in astrocytes.

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