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Statins Protect Against HIV‐1 and Amyloid beta‐Induced Barrier Dysfunction and Inflammatory Responses in an In Vitro Model of the Blood‐Brain Barrier
Author(s) -
ANDRAS IBOLYA E,
Rha GeunBae,
Huang Wen,
Eum SungYong,
Couraud PierreOlivier,
Hennig Bernhard,
Toborek Michal
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.734.13
Subject(s) - jurkat cells , blood–brain barrier , simvastatin , proinflammatory cytokine , in vitro , amyloid beta , beta (programming language) , amyloid (mycology) , inflammation , pharmacology , immunology , biology , chemistry , medicine , t cell , endocrinology , biochemistry , pathology , peptide , central nervous system , computer science , programming language , immune system
HIV‐1 infection and prolonged anti‐retroviral therapy were demonstrated to contribute to an increase in amyloid beta deposition in older HIV‐infected individuals. We hypothesize that amyloid beta and HIV‐1 can potentiate their toxic effects on the blood‐brain barrier. To study this hypothesis, we employed an in vitro model of human brain microvascular endothelial cells (HBMEC) co‐cultured with human Jurkat T cells or human monocytes infected with HIV‐1. The presence of HIV‐1 markedly increased fluorescent amyloid beta binding to HBMEC. Amyloid beta significantly amplified E‐selectin promoter activity in HBMEC in the presence of HIV‐1 infected Jurkat T cells. Simvastatin, the HMG‐CoA reductase inhibitor, protected against the increased E‐selectin promoter activity in HBMEC co‐cultured with HIV‐1‐infected Jurkat T cells. In addition, simvastatin reduced the adhesion and transmigration across the BBB of HIV‐1 infected monocytes exposed to amyloid beta. These results indicate that statins, such as simvastatin, may protect the blood‐brain barrier against the injuries and proinflammatory effects induced by HIV‐1 and amyloid beta. Supported by MH63022, MH072567, and NS39254.