Abstract
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
Substances
-
Endothelin-1
-
HIV Envelope Protein gp120
-
RNA, Messenger