HIV-1-induced production of endothelin-1 in an in vitro model of the human blood-brain barrier

Neuroreport. 2002 Jul 2;13(9):1179-83. doi: 10.1097/00001756-200207020-00022.


Evidence suggests that the HIV-1 envelope glycoproteins play a role in the central nervous system (CNS) complications of AIDS. Endothelin-1 (ET-1) has also been implicated in brain injury and the progression of the AIDS dementia complex (ADC). Here, we used a real-time reverse transcription polymerase chain reaction assay and an immunometric assay to show that in vitro model of the blood-brain barrier (BBB) consisting of a monolayer co-culture of astrocytes and human brain microvascular endothelial cells (A-HBMEC) increased its expression of ET-1 mRNA and secretion of ET-1 peptide when infected with HIV-1. The enhanced expression of ET-1 occurred independently of viral replication as it was also induced by the viral glycoprotein coat HIV-1g120SF. These results show that one mechanism by which HIV-1 might affect the CNS is by inducing release of ET-1 by the BBB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Dementia Complex / metabolism
  • AIDS Dementia Complex / physiopathology
  • AIDS Dementia Complex / virology*
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Astrocytes / virology*
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / immunology*
  • Cells, Cultured
  • Coculture Techniques
  • Dose-Response Relationship, Drug
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / virology*
  • Gene Expression Regulation, Viral / physiology
  • HIV Envelope Protein gp120 / metabolism*
  • HIV Envelope Protein gp120 / pharmacology
  • HIV-1 / metabolism*
  • HIV-1 / pathogenicity
  • Humans
  • Models, Biological
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation / drug effects
  • Up-Regulation / physiology


  • Endothelin-1
  • HIV Envelope Protein gp120
  • RNA, Messenger