Cocaine-induced HIV-1 expression in microglia involves sigma-1 receptors and transforming growth factor-beta1.
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.
Gekker
Genya
G
Center for Infectious Diseases and Microbiology Translational Research, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Hu
Shuxian
S
Sheng
Wen S
WS
Rock
R Bryan
RB
Lokensgard
James R
JR
Peterson
Phillip K
PK
D030201:Activin Receptors, Type I / Q000037:antagonists & inhibitors; D000906:Antibodies / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology; D005029:Ethylenediamines / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016655:HIV Core Protein p24 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D006801:Humans; D017628:Microglia / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D000097605:Sigma-1 Receptor
D030201:Activin Receptors, Type I; D000906:Antibodies; D001549:Benzamides; D003042:Cocaine; D004149:Dioxoles; D005029:Ethylenediamines; D016655:HIV Core Protein p24; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta; D017480:Receptors, sigma; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000097605:Sigma-1 Receptor; C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; C508960:TGFB1 protein, human; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin