Abstract
The neuropharmacological properties of cocaine are known to be associated with the activation of sigma-1 receptors. Cocaine also has been shown to alter both cytokine production and HIV-1 expression in mononuclear phagocytes, including microglial cells. This study tested the hypothesis that sigma-1 receptors and transforming growth factor (TGF)-beta1 are involved in cocaine-induced up-regulation of HIV-1 expression in microglial cell cultures. Treatment of microglial cells with cocaine resulted in a concentration-dependent increase in viral expression assessed by measurement of p24 antigen levels in culture supernatants. This cocaine-mediated stimulation of HIV-1 expression was blocked by treatment of microglia with inhibitors of sigma-1 receptors (BD1047) and TGF-beta1 (SB-431542 and anti-TGF-beta1 antibodies). Microglia were also shown to constitutively express sigma-1 receptor mRNA. Thus, the results of this study support the notion that neuroimmunopharmacological properties of cocaine involve sigma-1 receptors and cytokines.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Activin Receptors, Type I / antagonists & inhibitors
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Antibodies / pharmacology
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Benzamides / pharmacology
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Cells, Cultured
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Cocaine / pharmacology*
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Dioxoles / pharmacology
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Ethylenediamines / pharmacology
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Gene Expression / drug effects
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HIV Core Protein p24 / metabolism
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HIV-1 / drug effects*
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HIV-1 / immunology
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HIV-1 / physiology
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Humans
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Microglia / cytology
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Microglia / metabolism
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Microglia / virology*
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Protein Serine-Threonine Kinases
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Receptor, Transforming Growth Factor-beta Type I
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Receptors, Transforming Growth Factor beta / antagonists & inhibitors
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Receptors, sigma / antagonists & inhibitors
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Receptors, sigma / genetics
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Receptors, sigma / physiology*
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Sigma-1 Receptor
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Transforming Growth Factor beta / antagonists & inhibitors
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Transforming Growth Factor beta / immunology
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Transforming Growth Factor beta / physiology*
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Transforming Growth Factor beta1
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Up-Regulation / drug effects
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Up-Regulation / genetics
Substances
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4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
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Antibodies
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Benzamides
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Dioxoles
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Ethylenediamines
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HIV Core Protein p24
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Receptors, Transforming Growth Factor beta
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Receptors, sigma
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TGFB1 protein, human
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin
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Protein Serine-Threonine Kinases
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Activin Receptors, Type I
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Receptor, Transforming Growth Factor-beta Type I
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Cocaine