Martin-Kleiner Irena, Balog Tihomir, Gabrilovac Jelka
Division of Molecular Medicine, Ruder Bosković Institute, Zagreb, Croatia.
Neuroimmunomodulation. 2006;13(1):1-7. doi: 10.1159/000092107. Epub 2006 Apr 3.
New data regarding signal transduction triggered by opioid ligands in immune cells are reviewed, and the signal transduction in neuronal cells is documented. Similar signaling pathways are induced by opioids in immune as well as neuronal cells. Opioids altered second messenger cAMP, intracellular calcium, and second messenger-induced kinases in immune cells. Met-enkephalin, preferentially delta-opioid, was bimodally regulated, while kappa-opioids inhibited these second messengers. delta-, kappa- and micro-opioids altered nitric oxide secretion, inducing cGMP as the second messenger in immune cells. Coupling of opioid agonists to opioid receptors activated mitogen-activated protein/extracellular signal-regulated protein kinases and various transcription factors in immune cells. Activator protein 1 (AP-1), c-fos, and nuclear factor-kappaB (NF-kappaB) are transcription factors shared by neuronal and immune cells. Delta-opioids activated AP-1, c-fos, activating transcription factor 2, Ikaros-1 and Ikaros-2 transcription factors in immune cells. Induction of kappa-opioid receptor gene by retinoic acid resulted in increased binding of Sp1 transcription factor to the promoter of the kappa-opioid receptor. Micro-opioids inhibited synthesis of common transcription factors AP-1, c-fos, NF-kappaB, and nuclear factor of activated T cells in activated or stimulated immune cells, whereas micro-opioids activated NF-kappaB, GATA-3, and Kruppel-like factor 7 transcription factors in non-stimulated immune cells.
本文综述了免疫细胞中阿片样物质配体触发的信号转导的新数据，并记录了神经元细胞中的信号转导。阿片样物质在免疫细胞和神经元细胞中诱导相似的信号通路。阿片样物质改变了免疫细胞中的第二信使环磷酸腺苷（cAMP）、细胞内钙以及第二信使诱导的激酶。甲硫氨酸脑啡肽（Met-enkephalin），尤其是δ-阿片样物质，受到双峰调节，而κ-阿片样物质则抑制这些第二信使。δ-、κ-和μ-阿片样物质改变一氧化氮分泌，在免疫细胞中诱导环磷酸鸟苷（cGMP）作为第二信使。阿片样物质激动剂与阿片样物质受体的偶联激活了免疫细胞中的丝裂原活化蛋白/细胞外信号调节蛋白激酶以及各种转录因子。活化蛋白1（AP-1）、c-fos和核因子κB（NF-κB）是神经元和免疫细胞共有的转录因子。δ-阿片样物质激活了免疫细胞中的AP-1、c-fos、激活转录因子2、Ikaros-1和Ikaros-2转录因子。视黄酸诱导κ-阿片样物质受体基因导致Sp1转录因子与κ-阿片样物质受体启动子的结合增加。μ-阿片样物质在活化或刺激的免疫细胞中抑制常见转录因子AP-1、c-fos、NF-κB和活化T细胞核因子的合成，而μ-阿片样物质在未刺激的免疫细胞中激活NF-κB、GATA-3和Kruppel样因子7转录因子。
