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

Yong Song Ha, Jiyoon Ryu, Mi Ju Sung, Jin Park Lee, Ae Lee Ji, Young Choi Soo, Jinseu Park

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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-?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-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.

Original languageEnglish (US)
Pages (from-to)27-37
Number of pages11
JournalExperimental and Molecular Medicine
Volume39
Issue number1
DOIs
StatePublished - Feb 28 2007
Externally publishedYes

Keywords

  • Astrocytes
  • Cell adhesion molecules
  • Inflammation
  • Intercellular adhesion molecule-1
  • NF-κB
  • Reactive oxygen species
  • Tat protein, HIV-1
  • Vascular cell adhesion molecule-1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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