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PMID: 10982368 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Induction of the chemokines interleukin-8 and IP-10 by human immunodeficiency virus type 1 tat in astrocytes.

Journal of virology ·Vol. 74 ·No. 19 ·2000-10-00 ·Pages 9214-21

Kutsch O, Oh J, Nath A, Benveniste EN

Abstract

A finding commonly observed in human immunodeficiency virus type 1 (HIV-1)-infected patients is invasion of the brain by activated T cells and infected macrophages, eventually leading to the development of neurological disorders and HIV-1-associated dementia. The recruitment of T cells and macrophages into the brain is likely the result of chemokine expression. Indeed, earlier studies revealed that levels of different chemokines were increased in the cerebrospinal fluid of HIV-1-infected patients whereas possible triggers and cellular sources for chemokine expression in the brain remain widely undefined. As previous studies indicated that HIV-1 Tat, the retroviral transactivator, is capable of inducing a variety of cellular genes, we investigated its capacity to induce production of chemokines in astrocytes. Herein, we demonstrate that HIV-1 Tat(72aa) is a potent inducer of MCP-1, interleukin-8 (IL-8), and IP-10 expression in astrocytes. Levels of induced IP-10 protein were sufficiently high to induce chemotaxis of peripheral blood lymphocytes. In addition, Tat(72aa) induced IL-8 expression in astrocytes. IL-8 mRNA induction was seen less then 1 h after Tat(72aa) stimulation, and levels remained elevated for up to 24 h, leading to IL-8 protein production. Tat(72aa)-mediated MCP-1 and IL-8 mRNA induction was susceptible to inhibition by the MEK1/2 inhibitor UO126 but was only modestly decreased by the inclusion of the p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190. In contrast, Tat-mediated IP-10 mRNA induction was suppressed by SB202190 but not by the MEK1/2 inhibitor UO126. These findings indicate that MAPKs play a major role in Tat(72aa)-mediated chemokine induction in astrocytes.

MeSH Terms
Astrocytes/metabolism,virology Cells, Cultured Chemokine CCL2/metabolism Gene Products, tat/metabolism HIV Infections/metabolism HIV-1 Humans Interleukin-8/metabolism Receptors, Chemokine/metabolism tat Gene Products, Human Immunodeficiency Virus
Chemicals
Chemokine CCL2 Gene Products, tat Interleukin-8 Receptors, Chemokine tat Gene Products, Human Immunodeficiency Virus
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kutsch O
Department of Cell Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
Oh J
Nath A
Benveniste E N
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.74.19.9214-9221.2000
Published
2000-10-00
Pages
9214-21
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC102120
Subset
IM
Grants
NINDS NIH HHS · R01 NS036765 · United States
NIMH NIH HHS · MH55795 · United States
NINDS NIH HHS · NS29719 · United States
NINDS NIH HHS · NS36765 · United States
External Links
PubMed source DOI: 10.1128/jvi.74.19.9214-9221.2000 PMC Full Text View journal details
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