Inducible Expression of Functional Mu Opioid Receptors in Murine Dendritic Cells
Inducible Expression of Functional Mu Opioid Receptors in Murine Dendritic Cells
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DOI：
10.1007/s11481-009-9145-7
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发表时间：
2009-09-01
影响因子：
6.2
通讯作者：
Jiang, Xing-Hong
中科院分区：
文献类型：
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作者：
Li, Zheng-Hong;Chu, Niansheng;Jiang, Xing-Hong
阿片类药物对免疫系统有直接的影响，已有报道在多种免疫细胞上表达功能性阿片受体。树突状细胞(DC)是免疫反应的重要诱导者和调节者。在这项研究中，我们研究了小鼠树突状细胞是否表达功能性MU阿片受体(MOR)。RT-PCR和双重免疫荧光染色显示活化的小鼠树突状细胞中有MOR的表达。我们还研究了不同的Toll样受体配体对小鼠树突状细胞中MOR信使RNA的动态表达。在功能上，MOR的特异性激动剂内吗啡肽1(EM1)可抑制Forsklin诱导活化的DC中环磷酸腺苷水平的形成。此外，EM1处理导致脂多糖刺激的DC中p38MAPK的激活减少，ERK信号的激活增加。持续地，用EM1处理DC通过增加IL-10和降低IL-12和IL-23来改变细胞因子的产生。我们的结果表明，MOR可在活化的DC上诱导表达，并在功能上介导EM1诱导的DC效应。因此，树突状细胞可能参与了神经内分泌和免疫系统之间的串扰。
Opioids are known to exert direct effects on the immune system, and the expression of functional opioid receptors has been reported on several immune cell types. Dendritic cells (DCs) are important inducers and regulators of immune responses. In this study, we investigated whether murine dendritic cells express functional mu opioid receptors (MOR). RT-PCR analysis and double immunofluorescence staining revealed the expression of MOR in activated murine dendritic cells. We also studied the dynamic expression of MOR messenger RNA in murine dendritic cells in response to different Toll-like receptor ligands. Functionally, treatment of DCs with endomorphin 1 (EM1), a specific agonist of MOR, can inhibit the forskolin-induced formation of cyclic adenosine monophosphate level in activated DCs. Moreover, EM1 treatment resulted in less activation of p38 MAPK and more activation of ERK signaling in lipopolysaccharide-stimulated DCs. Consistently, treatment of DCs with EM1 altered cytokine production by increasing IL-10 and decreasing IL-12 and IL-23. Our results suggest that MOR is inducibly expressed on activated DCs and functionally mediates EM1-induced effects on DCs. Thus, dendritic cells might be involved in crosstalk between the neuroendocrine and the immune system.