HIV-1-induced production of endothelin-1 in an in vitro model of the human blood-brain barrier.
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.
Didier
Nathalie
N
CEA, Laboratoire d'Etudes du Métabolisme des Médicaments, Service de Pharmacologie et d'Immunologie, DRM/DSV, Bâtiment 136, 91191 Gif sur Yvette, France.
Banks
William A
WA
Créminon
Christophe
C
Dereuddre-Bosquet
Nathalie
N
Mabondzo
Aloïse
A
D015526:AIDS Dementia Complex / Q000378:metabolism / Q000503:physiopathology / Q000821:virology*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism* / Q000494:pharmacology; D015497:HIV-1 / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D008954:Models, Biological; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D019332:Endothelin-1; D015699:HIV Envelope Protein gp120; D012333:RNA, Messenger