Triptolide attenuates idiopathic pneumonia syndrome in a mouse bone marrow transplantation model by down-regulation of IL-17.
Triptolide attenuates idiopathic pneumonia syndrome in a mouse bone marrow transplantation model by down-regulation of IL-17.
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雷公藤甲素通过下调 IL-17 来减轻小鼠骨髓移植模型中的特发性肺炎综合征。
DOI：
10.1016/j.intimp.2012.09.016
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发表时间：
2012-12
影响因子：
5.6
通讯作者：
周浩
中科院分区：
文献类型：
--
作者：
周浩
特发性肺炎综合征（IPS）是骨髓移植（BMT）后患者的重要发病率和死亡率。然而，尚未确定可靠治疗IPS的有效疗法。先前使用小鼠BMT模型的研究表明，IFN-γ缺陷宿主中IPS的病理学涉及IL-17水平增加沿着供体T细胞募集到肺中。雷公藤内酯醇是一种从抗炎中草药中分离的有效免疫抑制化合物。雷公藤内酯醇可显著抑制T细胞产生IL-17，对自身免疫性疾病有免疫抑制作用。在本研究中，我们使用了一个特定的小鼠BMT模型（IFN-γ缺陷型B6到野生型B6 D2 F1）来评估雷公藤内酯醇对IPS发展的保护作用。我们观察到，与溶剂组相比，雷公藤内酯醇治疗后肺中的IL-17水平显著降低。此外，发现肺中Th 17细胞数量的减少与肺组织学损伤和肺功能障碍的改善相关。此外，IL-17的中和也显著减少IPS病理。本研究提示雷公藤甲素可显著抑制供体T细胞向肺内募集，从而有效预防骨髓移植后肺功能障碍。我们的研究可能为寻找适当的策略来预防IL-17介导的IPS和其他Th 17细胞介导的免疫病理学提供一些启示。
Idiopathic pneumonia syndrome (IPS) accounts for significant morbidity and mortality in patients following bone marrow transplantation (BMT). However, no effective therapy has been identified to reliably treat IPS. Previous studies using mouse BMT models suggest that the pathology of IPS in IFN-γ deficient host involves increased IL-17 levels along with recruitment of donor T cells into lung. Triptolide is a potent immunosuppressive compound isolated from an anti-inflammatory Chinese herbal medicine. Triptolide can significantly inhibit generation of IL-17 by T cells and mediate immunosuppressive effect on autoimmune disease. In the present study, we used a specific murine BMT model (IFN-γ deficient B6 to wildtype B6D2F1) to assess the protective effect of Triptolide on the development of IPS. We observed that IL-17 levels were significantly decreased in the lung after triptolide treatment compared with vehicle group. Furthermore, decreased number of Th17 cells in lung was found to be associated with amelioration of lung histological injury and pulmonary dysfunction. Additionally, neutralization of IL-17 also significantly reduced IPS pathology. Our study implied that triptolide could significantly inhibit donor T cell recruitment into lung, and thus prevent lung dysfunction after BMT usefully and effectively. Our study may shed some light on searching for proper strategies to prevent IL-17 mediated IPS and other Th17 cell-mediated immune pathologies.
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影响因子：
5.6
作者：
Hui Mao;Xue Chen;Qun Yi;Suyun Li;Zeng-li Wang;Fu-yu Li
通讯作者：
Hui Mao;Xue Chen;Qun Yi;Suyun Li;Zeng-li Wang;Fu-yu Li
DOI：
10.1016/s0162-3109(98)00036-8
发表时间：
1998-08
期刊：
Immunopharmacology
影响因子：
--
作者：
Yili Yang;Zhi-hong Liu;Eva Tolosa;Jun-wei Yang;Lei-shi Li
通讯作者：
Yili Yang;Zhi-hong Liu;Eva Tolosa;Jun-wei Yang;Lei-shi Li
影响因子：
20.3
作者：
Panoskaltsis-Mortari, A;Price, A;Blazar, BR
通讯作者：
Blazar, BR
影响因子：
6.2
作者：
Fidler, JM;Ku, GY;Chen, ZQ
通讯作者：
Chen, ZQ
影响因子：
20.3
作者：
Chen, X;Murakami, T;Howard, OMZ
通讯作者：
Howard, OMZ