Drug abuse and neuropathogenesis of HIV infection: role of DC-SIGN and IDO
| Autor: | Supriya D. Mahajan, Chubin Tsiao, Bindukumar B. Don Sykes, Madhavan Nair, Stanley A. Schwartz, Ram P. Chawda, Robert B. Whitney, Ross G. Hewitt |
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| Rok vydání: | 2004 |
| Předmět: |
Membrane permeability
Matrix Metalloproteinases Membrane-Associated Substance-Related Disorders Immunology HIV Infections Receptors Cell Surface Matrix metalloproteinase Blood–brain barrier Dioxygenases Immune system Cocaine medicine Immunology and Allergy Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Lectins C-Type RNA Messenger Anesthetics Local Cells Cultured ICAM-1 biology Dose-Response Relationship Drug Proteolytic enzymes Metalloendopeptidases Dendritic cell Dendritic Cells Matrix Metalloproteinases DC-SIGN medicine.anatomical_structure Neurology biology.protein Neurology (clinical) Cell Adhesion Molecules |
| Zdroj: | Journal of neuroimmunology. 157(1-2) |
| ISSN: | 0165-5728 |
| Popis: | Dendritic cells are the critical mediators of various immune responses and are the first line of defense against any infection including HIV. They play a major role in harboring HIV and the subsequent infection of T cells and passage of virus through the blood–brain barrier (BBB). The recently discovered DC-specific, CD4-independent HIV attachment receptor, DC-SIGN, and T-cell suppressing factor, indolamine 2,3-dioxygenase (IDO), are known to play a critical role in the immuno-neuropathogenesis of HIV infection. Since brain microvascular cells (BMVEC) express dendritic cell (DC)-specific C type ICAM-3 grabbing nonintegrin (DC-SIGN), it is possible that DC-SIGN may play a critical role in human immunodeficiency virus-type 1 (HIV-1) infection and migration of infected DC across BBB. Matrix metalloproteinases (MMPs) are proteolytic enzymes known to be responsible for maintenance, turnover and integrity of extracellular matrix. Our results show that cocaine upregulates IDO and DC-SIGN expression by DC. Further, cocaine upregulates DC-SIGN and MMPs in BMVEC supporting the hypothesis that cocaine causes membrane permeability facilitating endothelial transmigration of infected DC in to the CNS. Targeting DC-SIGN and IDO with specific monoclonal antibodies, inexpensive synthetic antagonists, antisense oligonucleotides and siRNA may lead to develop novel treatment strategies particularly in high-risk populations such as cocaine users. |
| Databáze: | OpenAIRE |
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