Regulatory effect of daphnetin, a coumarin extracted from Daphne odora, on the balance of Treg and Th17 in collagen-induced arthritis

Regulatory effect of daphnetin, a coumarin extracted from Daphne odora, on the balance of Treg and Th17 in collagen-induced arthritis
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瑞香素(一种从瑞香中提取的香豆素)对胶原诱导性关节炎中 Treg 和 Th17 平衡的调节作用

DOI:
10.1016/j.ejphar.2011.08.019
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发表时间:
2011-11-16
影响因子:
5
通讯作者:
Kuang, Nanzhen
Kuang, Nanzhen
中科院分区:
医学2区
文献类型:
--
作者:
Yao, Rongfeng;Fu, Yingyuan;Kuang, Nanzhen

文献摘要

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从瑞香中提取的瑞香素含有香豆素类化合物,具有镇痛和抗炎的作用。在本研究中,我们采用胶原诱导的关节炎大鼠模型,研究了瑞香素抗关节炎的作用及其对Tregs和Th17平衡的作用。用瑞香素治疗胶原性关节炎大鼠21 d。通过临床症状和组织病理学来评价瑞香素的治疗效果。ELISA法检测血清中Th17-、Treg-、Th2-、th1型细胞因子水平。采用免疫组化方法检测关节组织中相关受体ROR γ t、nf - κ B、Foxp3、CD77的表达水平。我们的研究结果显示,给药瑞香素可以明显减轻关节炎的严重程度,表现为降低关节炎评分,抑制炎症细胞的浸润,防止滑膜增生,从而导致关节炎大鼠的关节破坏。此外,瑞香素治疗降低了胶原诱导关节炎大鼠血清中Th17-、Th2-和th1型水平。相应的,给药后,胶原诱导的关节炎大鼠关节组织中ROR γ t、NF-kappa B和CD77的表达显著降低,Foxp3和IL-10的表达显著升高。总的来说,本研究表明,给药瑞香素减轻了关节炎关节的临床症状和病理破坏。治疗效果与Tregs上调,Th17-, Th2-和th1型细胞反应下调有关。这些结果为瑞香素通过调节Tregs和Th17的平衡来治疗自身免疫性关节炎提供了新的证据。(C) 2011 Elsevier B.V.版权所有
Daphnetin extracted from Daphne odora Var. marginata contains coumarin compounds, which possess properties of analgesic and anti-inflammatory effects. In this study, we investigated the therapeutic effect of daphnetin on anti-arthritis and its role on the balance of Tregs and Th17, using a collagen-induced arthritis rat model. Collagen-induced arthritis rats were treated with daphnetin for 21 days. The therapeutic effects of daphnetin were evaluated by clinical symptoms and histopathology. The levels of Th17-, Treg-, Th2-, Th1-type cytokines in serum were determined by ELISA. The expression levels of related receptors ROR gamma t, NF-kappa B, Foxp3 and CD77 in joint tissues were detected by immunohistochemistry. Our results showed that administration of daphnetin significantly alleviated the severity of the arthritis, as evidenced by the reduction of arthritis scores, suppression of the infiltration of inflammatory cells and prevention of synovial hyperplasia, thereby resulting in the joint destruction in the arthritis rats. Additionally, daphnetin treatment reduced the serum level of Th17-, Th2- and Th1-type in collagen-induced arthritis rats. Correspondingly, the expression of ROR gamma t, NF-kappa B and CD77 in joint tissue of collagen-induced arthritis rats was remarkably decreased, while the expression of Foxp3 and IL-10 was remarkably increased after being administered with daphnetin. Collectively, this study demonstrated that administration of daphnetin attenuated the clinical symptoms and pathological destruction of arthritis joints. The therapeutic effects were associated with the up-regulation of Tregs, down-regulation of Th17-, Th2- and Th1-type cell responses. The results provide novel evidence that daphnetin has therapeutic effects on autoimmune arthritis through modulating the balance of Tregs and Th17. (C) 2011 Elsevier B.V. All rights reserved.