HIV-1 tat protein induces the production of interleukin-8 by human brain-derived endothelial cells

This study focused on the role of the HIV-derived viral protein, tat, in ac tivating central nervous system (CNS)-derived endothelial cells (EC) to pro duce interleukin-8 (IL-8), a stimulator and chemoattractant for neutrophils and lymphocytes. Human CNS-EC treated with rat (100 ng/ml) demonstrated a 2 to 3 fold upregulation in IL-8 mRNA and protein. Tumor necrosis factor-al pha (TNF) and tat were found to act additively in upregulating IL-8 product ion. In contrast, transforming growth factor beta (TGF beta), appeared to d own modulate tat-induced IL-8 production. These data suggest that extracell ular tat, especially in the presence of TNF, may be responsible for the loc al production of IL-8. (C) 1999 Elsevier Science B.V. All rights reserved.