Shikonin inhibits maturation of bone marrow-derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma
Shikonin inhibits maturation of bone marrow-derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma
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DOI：
10.1111/j.1476-5381.2010.00972.x
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发表时间：
2010-12-01
影响因子：
7.3
通讯作者：
Cheng, Yu-Wen
中科院分区：
文献类型：
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作者：
Lee, Chen-Chen;Wang, Chien-Neng;Cheng, Yu-Wen
紫草素具有广泛的抗炎作用。在这里，我们评估了其对小鼠骨髓来源的树突状细胞（BM-DCs）的成熟和对小鼠哮喘模型的过敏反应的影响。实验方法培养的小鼠BM-DCs用于研究紫草素对细胞表面标志物的表达及其刺激T细胞增殖和细胞因子产生的影响。紫草素可剂量依赖性地抑制卵清蛋白（OVA; 100 mg.mL（-1））和胸腺基质淋巴细胞生成素（TSLP; 20 ng.mL（-1））诱导的BM-DCs表达主要组织相容性复合物II类、CD 80、CD 86、CCR 7和OX 40 L。紫草素处理的BM-DCs对CD（4+）T淋巴细胞的刺激作用较差，诱导应答T细胞释放的白细胞介素（IL）-4、IL-5、IL-13和肿瘤坏死因子（TNF）-α水平较低。在OVA免疫的小鼠中，经气管内滴注紫草素后，OVA激发诱导支气管肺泡灌洗液中IL-4、IL-5、IL-13、TNF-α和eotaxin的释放降低，降低肺细胞和纵隔淋巴结细胞IL-4和IL-5的产生，减轻OVA诱导的肺嗜酸性粒细胞增多和气道高反应性。DC在体外成熟并抑制哮喘小鼠模型的过敏性炎症和气道高反应性，显示出作为过敏性哮喘治疗的良好潜力。此外，我们的模型为筛选过敏性疾病的药物提供了一个新的平台。
BACKGROUND AND PURPOSEShikonin exhibits a wide range of anti-inflammatory actions. Here, we assessed its effects on maturation of murine bone marrow-derived dendritic cells (BM-DCs) and on allergic reactions in a murine model of asthma.EXPERIMENTAL APPROACHCultured murine BM-DCs were used to investigate the effects of shikonin on expression of cell surface markers and their stimulation of T-cell proliferation and cytokine production. The therapeutic potential of shikonin was evaluated in a model of allergic airway disease.KEY RESULTSShikonin dose-dependently inhibited expression of major histocompatibility complex class II, CD80, CD86, CCR7 and OX40L on BM-DCs, induced by a mixture of ovalbumin (OVA; 100 mg.mL(-1)) and thymic stromal lymphopoietin (TSLP; 20 ng.mL(-1)). Shikonin-treated BM-DCs were poor stimulators of CD(4+) T lymphocyte and induced lower levels of interleukin (IL)-4, IL-5, IL-13 and tumour necrosis factor (TNF)-alpha release by responding T-cells. After intratracheal instillation of shikonin in OVA-immunized mice, OVA challenge induced lower IL-4, IL-5, IL-13, TNF-alpha and eotaxin release in bronchial alveolar lavage fluid, lower IL-4 and IL-5 production in lung cells and mediastinal lymph node cells and attenuated OVA-induced lung eosinophilia and airway hyperresponsiveness.CONCLUSION AND IMPLICATIONSShikonin effectively suppressed OVA + TSLP-induced BM-DC maturation in vitro and inhibited allergic inflammation and airway hyperresponsiveness in a murine model of asthma, showing good potential as a treatment for allergic asthma. Also, our model provides a novel platform for screening drugs for allergic diseases.