Cocaine-induced HIV-1 expression in microglia involves sigma-1 receptors and transforming growth factor-beta1 |
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Authors: | Gekker Genya Hu Shuxian Sheng Wen S Rock R Bryan Lokensgard James R Peterson Phillip K |
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Affiliation: | Center for Infectious Diseases and Microbiology Translational Research, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA. |
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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. |
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