Gekker Genya, Hu Shuxian, Sheng Wen S, Rock R Bryan, Lokensgard James R, Peterson Phillip K
Center for Infectious Diseases and Microbiology Translational Research, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Int Immunopharmacol. 2006 Jun;6(6):1029-33. doi: 10.1016/j.intimp.2005.12.005. Epub 2006 Jan 13.
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.
可卡因的神经药理学特性已知与σ-1受体的激活有关。可卡因还被证明会改变单核吞噬细胞（包括小胶质细胞）中的细胞因子产生和HIV-1表达。本研究检验了以下假设：σ-1受体和转化生长因子（TGF）-β1参与可卡因诱导的小胶质细胞培养物中HIV-1表达的上调。用可卡因处理小胶质细胞导致通过测量培养上清液中的p24抗原水平评估的病毒表达呈浓度依赖性增加。用σ-1受体抑制剂（BD1047）和TGF-β1抑制剂（SB-431542和抗TGF-β1抗体）处理小胶质细胞可阻断这种由可卡因介导的HIV-1表达刺激。还显示小胶质细胞组成性表达σ-1受体mRNA。因此，本研究结果支持可卡因的神经免疫药理学特性涉及σ-1受体和细胞因子这一观点。
