Center for Substance Abuse Research, Center for Inflammation, Translational and Clinical Lung Research, Temple University School of Medicine, Philadelphia, PA 19140, USA.
J Neuroimmune Pharmacol. 2012 Dec;7(4):835-42. doi: 10.1007/s11481-012-9396-6. Epub 2012 Aug 25.
We have previously reported that functionally active μ-opioid receptors (MOR) are constitutively expressed at relatively low levels by developing T cells in the thymus. However, very little is known about the regulation of MOR expression by immature T cells. In this report, we first attempted to determine the effect of T cell receptor-induced T cell activation on the expression of MOR. We activated T cells with either the combination of anti-CD3 and CD28, or with superantigen, and observed a substantial increase in MOR transcript expression. We also chose to examine the effect of cytokine-mediated T cell activation on the expression of this opioid receptor. We selected certain cytokines that play a role in T cell development and are known to be present at functional levels in the thymus gland. Our results show that interferon γ (IFNγ), IL-1β, and IL-2, and in particular transforming growth factor-β (TGFβ), all induced significant increases in MOR transcript expression. On the other hand, both TNFα and IL-7 exhibited much weaker effects on MOR expression. These results show that MOR expression by developing T cells is strongly regulated by several cytokines involved in T cell development in the thymus gland.
我们之前曾报道过,功能性的 μ 阿片受体(MOR)在胸腺中发育的 T 细胞中以相对较低的水平持续表达。然而,对于不成熟 T 细胞中 MOR 表达的调控,我们知之甚少。在本报告中,我们首先试图确定 T 细胞受体诱导的 T 细胞激活对 MOR 表达的影响。我们通过使用抗-CD3 和 CD28 的组合或超抗原激活 T 细胞,观察到 MOR 转录物表达的显著增加。我们还选择研究细胞因子介导的 T 细胞激活对该阿片受体表达的影响。我们选择了某些在 T 细胞发育中起作用的细胞因子,并且已知这些细胞因子在胸腺中以功能性水平存在。我们的结果表明,干扰素 γ(IFNγ)、IL-1β 和 IL-2,特别是转化生长因子-β(TGFβ),均诱导了 MOR 转录物表达的显著增加。另一方面,TNFα 和 IL-7 对 MOR 表达的影响要弱得多。这些结果表明,胸腺中参与 T 细胞发育的几种细胞因子强烈调节发育中的 T 细胞中 MOR 的表达。