Suppression of HIV-1 Tat-induced monocyte adhesiveness by a cell-permeable superoxide dismutase in astrocytes

adhesion molecule-1; Tat, transactivator of transcription; ROS, reactive oxygen species; VCAM-1, vascular cell adhesion molecule-1 HIV-1 Tat is considered to be one of key players to facili-tate monocyte entry into the CNS, which is character-istic feature of AIDS-related encephalitis and de-mentia. This study was performed to determine the reg-ulatory function of superoxide dismutase (SOD) on the HIV-1 Tat-induced signaling pathways leading to NF-κB activation, expression of adhesion molecules, and monocyte adhesion in CRT-MG human as-troglioma cells by using cell-permeable SOD. When cell-permeable SOD was added to the culture medium of CRT-MG cells, it rapidly entered the cells in dose- and time-dependent manners. Treatment of astrocytes with cell-permeable SOD led to decrease in Tat-in-duced ROS generation as well as NF-κB activation. Cell-permeable SOD inhibited the activation of MAP kinases including ERK, JNK and p38 by HIV-1 Tat. Treatment of CRT-MG cells with cell-permeable SOD significantly inhibited protein and mRNA levels of ICAM-1 and VCAM-1 up-regulated by HIV-1 Tat, as measured by Western blot analysis and RT-PCR. Furthermore, enhanced adhesiveness of monocyte to astrocyte by HIV-1 Tat was significantly abrogated by pretreatment with cell-permeable SOD fusion pro-teins. These data indicate that SOD has a regulatory function for HIV-1 Tat-induced NF-κB activation in as-trocytes and suggest that cell-permeable SOD can be used as a feasible therapeutic agent for regulation of ROS-related neurological diseases