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 language | English (US) |
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Pages (from-to) | 1029-1033 |
Number of pages | 5 |
Journal | International Immunopharmacology |
Volume | 6 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2006 |
Bibliographical note
Funding Information:This work was supported by U.S. Public Health Service grant DA-09789. The authors are grateful to Dr. Fred Kravitz for his invaluable assistance.
Keywords
- Cocaine
- HIV-1
- Microglia
- Sigma-1 receptor
- Transforming growth factor-β1