Regulation of mu-opioid receptors by cytokines.
Regulation of mu-opioid receptors by cytokines.
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DOI：
10.2741/s16
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发表时间：
2009-06-01
期刊：
影响因子：
--
通讯作者：
Kraus, Jurgen
中科院分区：
文献类型：
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作者：
Kraus, Jurgen
阿片类药物是最有效的镇痛药。然而，它们的临床使用受到呼吸抑制等副作用和滥用可能性的限制。此外，它们还调节免疫功能并引起免疫抑制。临床上重要的阿片类药物（如吗啡）的作用是由 mu-阿片类受体介导的。了解控制神经元和免疫细胞中 mu-阿片受体基因表达的机制对于了解该受体的动态和活性至关重要。细胞因子是通常从免疫系统细胞释放的介质，是 mu-阿片受体基因表达的有效调节剂。这强调了 mu-阿片受体在神经免疫串扰中的重要性及其作为此类相互作用的分子基础的作用。本文将总结白细胞介素1、白细胞介素4、白细胞介素6和肿瘤坏死因子对神经元和免疫效应细胞中人μ阿片受体基因表达的上调，以及干扰素γ和粒细胞/巨噬细胞集落刺激因子的下调，以及转录因子启动子相互作用等分子机制。此外，还将讨论这些调节事件的生理重要性。
Opioids are the most potent analgesics. However, their clinical use is limited by side effects like respiratory depression and their high potential for abuse. In addition, they modulate immune functions and cause immunosuppression. Effects of clinically important opioids like morphine are mediated by the mu-opioid receptor. Knowledge about the mechanisms controling the expression of the mu-opioid receptor gene in neuronal and immune cells is crucial to understand the dynamics and the activity of this receptor. Cytokines, mediators typically released from cells of the immune system, are potent regulators of mu-opioid receptor gene expression. This emphazises the importance of mu-opioid receptors in the neuro-immune-crosstalk and their role as a molecular basis for such interactions. In this review, the up-regulation of human mu-opioid receptor gene expression in neuronal and immune effector cells by interleukin-1, interleukin-4, interleukin-6 and tumor necrosis factor, as well as its down-regulation by interferon-gamma and granulocyte/macrophage colony-stimulating factor will be summarized along with molecular mechanisms, such as transcription factor-promoter-interactions. In addition, the physiological importance of these regulatory events will be discussed.