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

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-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 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-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 generation by 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 increasing expression of adhesion molecules such as ICAM-1 and VCAM-1 via ROS-and NF-κB-dependent mechanisms in astrocytes.

Rutin inhibits osteoclast formation by decreasing reactive oxygen species and TNF-α by inhibiting activation of NF-κB

“…We showed that rutin attenuated ROS production by RANKL or RANKL/TNF and reduced NF-κB activation in osteoclast precursor cells. The involvement of ROS in NF-κB activation has also been demonstrated in other cell types (Schreck et al, 1991;Rhee, 1999;Droge, 2002;Song et al, 2007). Since NF-κB activation is critical for RANKL-induced osteoclastogenesis, it is plausible that the inhibitory effect of rutin on osteoclastogenesis should be mediated by suppression of NF-κB activation.…”

Endothelial ICAM-1 Protein Induction Is Regulated by Cytosolic Phospholipase A2α via Both NF-κB and CREB Transcription Factors

“…ously, CREB transcription factor undergoes activation by PKAdependent phosphorylation on Ser 133 (42), whereas p65 NF-kB RelA is phosphorylated by PKA on Ser 276 (42,43) or by a redoxsensitive mechanism on Ser 536 (44)(45)(46). The present study demonstrates a PKA-dependent phosphorylation of CREB on Ser 133 at 10 h and two events of phosphorylation of p65 NF-kB on Ser 536 at 1 h and 8-10 h of TNF-a exposure, whereas phosphorylation of p65 NF-kB Ser 276 was not detected under these conditions, suggesting that PKA is not involved in NF-kB activation.…”

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

“…Stimulation of astrocytes with HIV-1 Tat resulted in activation of NF-κB which was responsible for up-regulation of various cytokines, chemokines and adhesion molecules (Nicolini et al, 2001;Song et al, 2007). Although the mechanisms of Tat-mediated NF-κB activation remain to be elucidated, several studies have implicated the in-volvement of Tat-induced oxidative stress (Bruce- Keller et al, 2001;Song et al, 2007).…”

“…Although the mechanisms of Tat-mediated NF-κB activation remain to be elucidated, several studies have implicated the in-volvement of Tat-induced oxidative stress (Bruce- Keller et al, 2001;Song et al, 2007). HIV-1 Tat can increase levels of reactive oxygen species (ROS) directly and indirectly which in turn activates NF-κB, a redox-sensitive transcriptional factor.…”

“…HIV-1 Tat (transactivator of transcription) protein, which can be secreted from the infected cells, has the ability to enter uninfected cells and exert its activity on the expression of various adhesion molecules including vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in human endothelial cells and astrocytes (Dhawan et al, 1997;Woodman et al, 1999;Song et al, 2007). Up-regulation of expression of adhesion molecules such as ICAM-1 and VCAM-1 by HIV-1 Tat may induce a series of interactions between monocytes, endothelial cells, and astrocytes, facilitating infiltration of monocytes into the CNS (Rappaport et al, 1999;Langford and Masliah, 2001).…”