Extracellular HIV-1 Tat enhances monocyte adhesion by up-regulation of ICAM-1 and VCAM-1 gene expression via ROS-dependent NF-kappaB activation in astrocytes .
- Author:
Ha Yong SONG
1
;
Jiyoon RYU
;
Sung Mi JU
;
Lee Jin PARK
;
Ji Ae LEE
;
Soo Young CHOI
;
Jinseu PARK
Author Information
1. Department of Biomedical Science, Hallym University, Chuncheon 200-702, Korea. jinpark@hallym.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
astrocytes;
cell adhesion molecules;
inflammation;
intercellular adhesion molecule-1;
NF-kappaB;
reactive oxygen species;
Tat protein, HIV-1;
vascular cell adhesion molecule-1
- MeSH:
Vascular Cell Adhesion Molecule-1/genetics/*metabolism;
Up-Regulation/*drug effects;
Transcription, Genetic/genetics;
Reactive Oxygen Species/*metabolism;
NF-kappa B/*metabolism;
Monocytes/cytology/*drug effects/metabolism;
Intercellular Adhesion Molecule-1/genetics/*metabolism;
Humans;
*HIV-1;
Gene Products, tat/*pharmacology;
Cell Line;
Cell Adhesion/drug effects;
Astrocytes/cytology/metabolism
- From:Experimental & Molecular Medicine
2007;39(1):27-37
- CountryRepublic of Korea
- Language:English
-
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-kappaB 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-kappaB in astrocytes. Treatment of CRT-MG with NF-kappaB 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-kappaB 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-kappaB-dependent mechanisms in astrocytes.
