Transfection of human endothelial cells with HIV-1 tat gene activates NF-κB and enhances monocyte adhesion

Galen M. Pieper*, Cara L. Olds, Jeffrey D. Bub, Paul F Lindholm

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Human immunodeficiency virus (HIV)-1 Tat released from HIV-1-infected monocytes is believed to enter other cells via an integrin-facilitated pathway, resulting in altered gene expression. Indeed, exogenous Tat protein can increase cell adhesion molecule gene expression in human endothelial cells. Signaling pathways initiated by Tat in endothelial cells are not known. We evaluated the ability of endogenous tat to stimulate monocyte adhesion via activation of nuclear factor-κB (NF-κB-within human umbilical vein endothelial cells. Transfection with pcTat, but not control vector DNA, increased NF-κB binding activity, NF-κB luciferase reporter activity, and monocyte adhesion. pcTat also increased κB-dependent HIV-1-LTR-CAT reporter activity 28-fold compared with a 3-fold increase produced by transfection with an equivalent amount of pcTax (from human leukemia virus). The pcTat-induced increase in pNF-κB-Luc activity and monocyte adhesion to endothelial cells was blocked by cotransfection with dominant-negative mutant IκBα and by incubation with 10 mM aspirin. We conclude that monocyte adhesion to human endothelial cells stimulated by pcTat is mediated via an NF-κB-dependent mechanism. Furthermore, inhibition studies using aspirin suggest that pcTat-stimulated NF-κB activation and monocyte adhesion occur via a redox-sensitive mechanism.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number6 52-6
StatePublished - Dec 1 2002

Keywords

  • Cell adhesion
  • Endothelium
  • Human immunodeficiency virus
  • Nuclear factor-κB
  • Signal transduction
  • Viral protein

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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