Sharp B M, Li M D, Matta S G, McAllen K, Shahabi N A
Department of Pharmacology, University of Tennessee, 874 Union Avenue, Crowe Bldg., Memphis, TN 38163, USA.
Ann N Y Acad Sci. 2000;917:764-70. doi: 10.1111/j.1749-6632.2000.tb05441.x.
Delta opioid receptors (DORs) and preproenkephalin-A-derived opiate peptides are expressed by mononuclear cells in various lymphoid organs. DOR ligands modulate a variety of immune functions, such as T-cell proliferation, calcium mobilization, and cytokine production. Recently, quiescent T cells were found to express low levels of DOR transcripts, which increased due to the following: cell culture of unstimulated murine splenocytes (depending on cell density); cross-linking the T-cell receptor (TCR) with anti-CD3-epsilon; and a single in vivo exposure to staphylococcal enterotoxin B (SEB). Enhanced expression of DOR mRNA was mediated transcriptionally. Moreover, PMA + ionomycin, which mimic the proliferative signal of anti-CD3, inhibited the expression of DOR mRNA. Using semiquantitative immunofluorescence to detect DORs, SEB was found to increase the fraction of T cells that expressed DOR and to enhance the relative level of DOR expression per T cell. Previous studies have shown that DOR agonists inhibited the anti-CD3-stimulated production of interleukin-2 and T-cell proliferation. Therefore, the enhanced expression of DORs by activated T cells may be capable of downregulating the T-cell activation program.
δ阿片受体(DORs)和前脑啡肽原A衍生的阿片肽由各种淋巴器官中的单核细胞表达。DOR配体调节多种免疫功能,如T细胞增殖、钙动员和细胞因子产生。最近发现,静止T细胞表达低水平的DOR转录本,在以下情况下其水平会升高:未刺激的小鼠脾细胞进行细胞培养(取决于细胞密度);用抗CD3-ε交联T细胞受体(TCR);以及单次体内暴露于葡萄球菌肠毒素B(SEB)。DOR mRNA表达的增强是由转录介导的。此外,模拟抗CD3增殖信号的佛波酯(PMA)+离子霉素抑制了DOR mRNA的表达。使用半定量免疫荧光检测DORs,发现SEB增加了表达DOR的T细胞比例,并提高了每个T细胞DOR表达的相对水平。先前的研究表明,DOR激动剂抑制抗CD3刺激的白细胞介素-2产生和T细胞增殖。因此,活化T细胞中DORs表达的增强可能能够下调T细胞活化程序。