Abstract
We report that cocaine may act as cofactor in HIV pathogenesis by increasing dendritic cell-specific C type ICAM-3-grabbing nonintegrin (DC-SIGN) expression on dendritic cells (DC). Our results show that cocaine-using, long-term nonprogressors and normal progressors of HIV infection manifest significantly higher levels of DC-SIGN compared with cocaine-nonusing long-term nonprogressors and normal progressors, respectively. Furthermore, in vitro HIV infection of MDC from normal subjects cultured with cocaine and/or HIV peptides up-regulated DC-SIGN, confirming our in vivo finding. Cocaine, in synergy with HIV peptides, also up-regulates DC-SIGN gene expression by MDC. Furthermore, the cocaine-induced effects were reversed by a D1 receptor antagonist demonstrating the specificity of the reaction. Our results indicate that cocaine exacerbates HIV infection by up-regulating DC-SIGN on DC and these effects are mediated via dysregulation of MAPKs. These data are the first evidence that cocaine up-regulates the expression of DC-SIGN on DC. A better understanding of the role of DC-SIGN in HIV infection may help to design novel therapeutic strategies against the progression of HIV disease in the drug-using population.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antigens, CD / metabolism*
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Cell Adhesion Molecules / biosynthesis*
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Cell Adhesion Molecules / genetics
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Cell Differentiation / drug effects
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Cell Differentiation / immunology
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Cocaine / pharmacology*
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Dendritic Cells / drug effects*
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Dendritic Cells / virology
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Dopamine Antagonists / pharmacology
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Drug Synergism
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / immunology
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Gene Products, tat / pharmacology
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HIV Envelope Protein gp120 / pharmacology
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HIV Infections / enzymology
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HIV Infections / immunology*
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HIV Infections / metabolism*
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HIV Infections / pathology
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HIV-1 / drug effects
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HIV-1 / immunology*
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Humans
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Lectins, C-Type / biosynthesis*
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Lectins, C-Type / genetics
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / immunology
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / physiology
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Receptors, Cell Surface / biosynthesis*
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Receptors, Cell Surface / genetics
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Receptors, Dopamine / metabolism
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Virus Replication / drug effects
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Virus Replication / immunology
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tat Gene Products, Human Immunodeficiency Virus
Substances
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Antigens, CD
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CLEC4M protein, human
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Cell Adhesion Molecules
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DC-specific ICAM-3 grabbing nonintegrin
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Dopamine Antagonists
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Gene Products, tat
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HIV Envelope Protein gp120
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ICAM3 protein, human
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Lectins, C-Type
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Receptors, Cell Surface
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Receptors, Dopamine
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tat Gene Products, Human Immunodeficiency Virus
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Mitogen-Activated Protein Kinases
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Cocaine