Börner Christine, Höllt Volker, Kraus Jürgen
Department of Pharmacology and Toxicology, University of Magdeburg, Magdeburg, Germany.
Neuroimmunomodulation. 2007;14(6):281-6. doi: 10.1159/000117809. Epub 2008 Feb 21.
Effects of cannabinoids are mediated by CB1 and CB2 receptors. In addition to neuronal effects, cannabinoids are potent modulators of immune functions. In this report, we investigated whether the transcription of these receptors is regulated after activation of T lymphocytes.
CB1- and CB2-specific mRNA of primary human peripheral blood T cells and cells of the human T cell line Jurkat was measured by quantitative real-time RT-PCR in response to CD3/28. Using the decoy oligonucleotide approach, transcription factors involved in the regulation were determined. A promoter analysis was performed using transient transfection of chloramphenicol acetyl transferase reporter gene constructs in Jurkat cells.
Activation of human T cells caused an induction of CB1 mRNA expression in primary human T cells (8-fold) and Jurkat cells (29-fold). In contrast, CB2 transcription was not regulated. The CD3/28-mediated upregulation of CB1 involves the transcription factors AP-1, NF kappaB and NFAT. Furthermore, 2,490 bp of the CB1 promoter mediated inducibility in response to CD3/28.
The upregulation of CB1 in activated T cells, together with the constitutive expression of CB2, enables cellular responses to cannabinoids mediated by both receptor subtypes. It may thus contribute to the understanding of the various modulatory effects of cannabinoids on activated T cells.
大麻素的作用由CB1和CB2受体介导。除了对神经元的作用外，大麻素还是免疫功能的强效调节剂。在本报告中，我们研究了T淋巴细胞激活后这些受体的转录是否受到调控。
通过定量实时逆转录聚合酶链反应（RT-PCR）检测人外周血原代T细胞和人T细胞系Jurkat细胞中CB1和CB2特异性mRNA对CD3/28的反应。使用诱饵寡核苷酸方法确定参与调控的转录因子。在Jurkat细胞中通过瞬时转染氯霉素乙酰转移酶报告基因构建体进行启动子分析。
人T细胞的激活导致人外周血原代T细胞（8倍）和Jurkat细胞（29倍）中CB1 mRNA表达的诱导。相比之下，CB2转录不受调控。CD3/28介导的CB1上调涉及转录因子AP-1、核因子κB（NFκB）和活化T细胞核因子（NFAT）。此外，CB1启动子的2490 bp介导了对CD3/28的诱导性。
活化T细胞中CB1的上调，以及CB2的组成性表达，使得细胞能够对两种受体亚型介导的大麻素产生反应。因此，这可能有助于理解大麻素对活化T细胞的各种调节作用。
