Gongora Celine, Hose Stacey, O'Brien Terrence P, Sinha Debasish
Institut de Biotechnologie et Pharmacologie, CNRS UMR 5094, Montpellier, Cedex 5, France.
Immunol Lett. 2004 Jan 30;91(1):11-6. doi: 10.1016/j.imlet.2003.09.006.
Cannabinoid receptors are known to be expressed in microglia; however, their involvement in specific aspects of microglial immune function has not been demonstrated. Many effects of cannabinoids are mediated by two G-protein coupled receptors, designated CB1 and CB2. We have shown that the CB1 receptor is expressed in microglia that also express MHC class II antigen (J. Neuroimmunol. 82 (1998) 13-21). In our present study, we have analyzed the effect of cannabinoid agonist CP55,940 on MHC class II expression on the surface of IFN-gamma induced microglial cells by flow cytometry. CP55,940 blocked the class II MHC expression induced by IFN-gamma. It has been shown that the regulation of class II MHC genes occurs primarily at the transcriptional level, and a non-DNA binding protein, class II transactivator (CIITA), has been shown to be the master activator for class II transcription. We find that mRNA levels of CIITA are increased in IFN-gamma induced EOC 20 microglial cells and that this increase is almost entirely eliminated by the cannabinoid agonist CP55,940. These data suggests that cannabinoids affect MHC class II expression through actions on CIITA at the transcriptional level.
已知大麻素受体在小胶质细胞中表达；然而，它们在小胶质细胞免疫功能特定方面的作用尚未得到证实。大麻素的许多作用是由两种G蛋白偶联受体介导的，分别称为CB1和CB2。我们已经表明，CB1受体在同时表达MHC II类抗原的小胶质细胞中表达（《神经免疫学杂志》82 (1998) 13 - 21）。在我们目前的研究中，我们通过流式细胞术分析了大麻素激动剂CP55,940对IFN-γ诱导的小胶质细胞表面MHC II类表达的影响。CP55,940阻断了IFN-γ诱导的II类MHC表达。已经表明，II类MHC基因的调控主要发生在转录水平，并且一种非DNA结合蛋白，即II类反式激活因子（CIITA），已被证明是II类转录的主要激活因子。我们发现，在IFN-γ诱导的EOC 20小胶质细胞中，CIITA的mRNA水平升高，并且这种升高几乎完全被大麻素激动剂CP55,940消除。这些数据表明，大麻素通过在转录水平上作用于CIITA来影响MHC II类表达。
