Induction of the Chemokines Interleukin-8 and IP-10 by Human Immunodeficiency Virus Type 1 Tat in Astrocytes

• DOI: 10.1128/jvi.74.19.9214-9221.2000
• Publication Date: 2002-07-27T10:06:23Z
• Authors: O. Kutsch; J.-W. Oh; A. Nath; E. N. Benveniste
• Keywords: Neuroglia

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