Suppression of HIV-1 Tat-induced monocyte adhesiveness by a cell-permeable superoxide dismutase in astrocytes.
- Author:
Ha Yong SONG
1
;
Sung Mi JU
;
Ji Ae LEE
;
Hyung Joo KWON
;
Won Sik EUM
;
Sang Ho JANG
;
Soo Young CHOI
;
Jinseu PARK
Author Information
1. 1Department of Biomedical Science, College of Natural Sciences, Hallym University, Chuncheon 200-702, Korea. jinpark@hallym.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
cell adhesion;
gene products, tat;
HIV;
inflammation;
intercellular adhesion molecule-1;
NF-kappaB;
reactive oxygen species;
superoxide dismutase;
vascular cell adhesion molecule-1
- MeSH:
Astrocytes/*enzymology;
Cell Adhesion/*physiology;
Cell Membrane Permeability;
Gene Products, tat/*pharmacology;
HIV Infections/metabolism;
HIV-1/*chemistry;
Humans;
Monocytes/cytology/*drug effects;
Signal Transduction;
Superoxide Dismutase/genetics/*physiology
- From:Experimental & Molecular Medicine
2007;39(6):778-786
- CountryRepublic of Korea
- Language:English
-
Abstract:
HIV-1 Tat is considered to be one of key players to facilitate monocyte entry into the CNS, which is characteristic feature of AIDS-related encephalitis and dementia. This study was performed to determine the regulatory function of superoxide dismutase (SOD) on the HIV-1 Tat-induced signaling pathways leading to NF-kappaB activation, expression of adhesion molecules, and monocyte adhesion in CRT-MG human astroglioma 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-induced ROS generation as well as NF-kappaB 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 proteins. These data indicate that SOD has a regulatory function for HIV-1 Tat-induced NF-kappaB activation in astrocytes and suggest that cell-permeable SOD can be used as a feasible therapeutic agent for regulation of ROS-related neurological diseases.
