Dextromethorphan inhibits activations and functions in dendritic cells.

Dextromethorphan inhibits activations and functions in dendritic cells.
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DOI:
10.1155/2013/125643
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发表时间:
2013
影响因子:
--
通讯作者:
Lin CC
Lin CC
中科院分区:
其他
文献类型:
--
作者:
Chen DY;Song PS;Hong JS;Chu CL;Pan IH;Chen YM;Lin CH;Lin SH;Lin CC

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树突状细胞(DC)在连接天然免疫和获得性免疫中起着重要作用。因此,树突状细胞被认为是免疫调节剂开发的主要靶点。在这项研究中,我们检测了右美沙芬(DXM),一种常见的高安全性止咳药,对DC的激活和功能的影响。地塞米松可显著抑制脂多糖诱导的小鼠骨髓树突状细胞(BMDCs)共刺激分子的表达。此外,地塞米松治疗减少了脂多糖激活的成熟BMDCs中活性氧物种(ROS)、促炎细胞因子和趋化因子的产生。因此,地塞米松取消了脂多糖刺激的DC诱导抗原特异性T细胞激活的能力,这一能力取决于它们在混合白细胞培养中的增殖和干扰素-γ的分泌减少。此外,地塞米松对BMDCs的抑制作用可能与抑制脂多糖诱导的丝裂原活化和核因子-κB转位有关。地塞米松显著降低内毒素诱导的人单核细胞来源的树突状细胞(MDDC)表面CD80、CD83和HLA-DR的表达以及IL-6和IL-12的分泌。这些发现为DXM治疗对DC的影响提供了新的见解,并提示DXM有可能用于治疗DC相关的急慢性疾病。
Dendritic cells (DCs) play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM), a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs) was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS), proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN-γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF-κB translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs). These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases.
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