Cocaine-induced HIV-1 expression in microglia involves sigma-1 receptors and transforming growth factor-β1

Genya Gekker, Shuxian Hu, Wen Sheng, R B Rock, James R Lokensgard, Phillip K. Peterson

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

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)-β1 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-β1 (SB-431542 and anti-TGF-β1 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.

Original languageEnglish (US)
Pages (from-to)1029-1033
Number of pages5
JournalInternational Immunopharmacology
Volume6
Issue number6
DOIs
StatePublished - Jun 1 2006

Keywords

  • Cocaine
  • HIV-1
  • Microglia
  • Sigma-1 receptor
  • Transforming growth factor-β1

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