Isorhamnetin, the active constituent of a Chinese herb Hippophae rhamnoides L, is a potent suppressor of dendritic-cell maturation and trafficking
Isorhamnetin, the active constituent of a Chinese herb Hippophae rhamnoides L, is a potent suppressor of dendritic-cell maturation and trafficking
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异鼠李素是中药沙棘的活性成分，是树突状细胞成熟和运输的有效抑制剂
DOI：
10.1016/j.intimp.2017.12.014
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发表时间：
2018
影响因子：
5.6
通讯作者：
Sun Erwei
中科院分区：
文献类型：
--
作者：
Shi Hui;He Juan;Li Xing;Han Jiaochan;Wu Riga;Wang Dantong;Yang Fangyuan;Sun Erwei
树突状细胞(DC)在连接天然免疫和获得性免疫方面具有重要作用，已被公认为免疫抑制治疗的主要靶点。异鼠李素(Isorhamnetin，Iso)是从中草药沙棘中提取的最常见的黄酮类化合物之一，已被证明在多种慢性炎症条件下具有抗炎、抗癌和抗氧化活性，但Iso对树突状细胞的作用尚未见报道。在这里，我们研究了Iso对骨髓来源的DC(BMDCs)的作用和机制，包括成熟、吞噬和运输。结果表明，Iso通过下调肿瘤坏死因子α、IL-6、IL-1β和IL-12p70的表达，上调IL-10的表达，抑制共刺激分子CD_(40)、CD_(80)和CD_(86)的表达，有效地抑制脂多糖诱导的BMDCs的成熟，而对吞噬功能无明显影响。此外，Iso还可通过抑制趋化因子受体7(CCR7)的表达而抑制脂多糖诱导的BMDCs的迁移。这些发现有力地表明，Iso是一种有效的免疫抑制剂，通过抑制DC的激活和运输，可用于预防或治疗慢性炎症、自身免疫性疾病和移植物排斥反应。
Dendritic cells (DCs) have been recognized as major targets of immunosuppressive therapies for their significant roles in connecting innate and adaptive immunity. Isorhamnetin (Iso), one of the most common flavonoid compounds extracted from the Chinese herbHippophae rhamnoidesL, has been proved to have anti-inflammatory, anticarcinogenic, and antioxidant activities in many chronic inflammatory conditions, but the effects of Iso on DCs have rarely been reported before. Here we investigated the functions and the mechanisms of Iso on bone marrow-derived DCs (BMDCs) including maturation, phagocytosis, and trafficking. Our data showed that Iso effectively inhibited the maturation of lipopolysaccharide (LPS)-treated BMDCs by down regulation of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and IL-12p70, up regulation of IL-10, and depression of costimulatory molecules CD40, CD80, and CD86, while had no effects on phagocytosis. Furthermore, Iso inhibited the migration of LPS-treated BMDCs, which may be due to its inhibition on chemokine receptor 7 (CCR7) expression. These findings strongly suggest that Iso is a potent immunosuppressive agent by inhibiting DC activation and trafficking, and may be used to prevent or treat chronic inflammation, autoimmune diseases, and graft rejections.