Gu-Ben-Fang-Xiao attenuates allergic airway inflammation by inhibiting BAFF-mediated B cell activation
Gu-Ben-Fang-Xiao attenuates allergic airway inflammation by inhibiting BAFF-mediated B cell activation
复制标题
Gu-Ben-Fang-Xiao 通过抑制 BAFF 介导的 B 细胞激活来减轻过敏性气道炎症
DOI：
10.1016/j.biopha.2020.110801
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发表时间：
2020-12-01
影响因子：
7.5
通讯作者：
Zhao, Xia
中科院分区：
文献类型：
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作者：
Liang, Zhong-Qing;Tu, Peng-Cheng;Zhao, Xia
过敏性气道炎症是哮喘发生发展的主要病理过程之一。B细胞激活因子（BAFF）介导的B细胞异常激活在过敏性气道炎症的发生中发挥关键作用。本研究观察了防治过敏性哮喘的中药复方固本防哮汤对过敏性气道炎症及BAFF介导的B细胞活化的影响。采用OVA-严重呼吸道合胞病毒（RSV）诱导的哮喘小鼠模型，在哮喘缓解期灌胃给药4周，观察其肺功能变化。HE染色观察肺组织病理变化，酶联免疫吸附法检测血清中IgE、BAFF和炎症因子水平。Western blotting和RT-qPCR检测BAFF、APRIL及其相关受体在肺、脾组织中的表达。流式细胞术检测脾脏、PBC中B细胞亚群和支气管肺泡灌洗液（BALF）中单核细胞亚群。结果表明：固复消汤能改善OVA-RSV致敏小鼠的肺功能，减轻肺组织的炎症改变，降低OVA-RAV小鼠血清中IL-6、TNF-α、IL 1-β、INOS、IL 13及IL-15、IgE、BAFF水平。此外，固本活血汤还能显著降低小鼠PBC和脾细胞中CD 19 + CD 27 + B细胞亚群和IgE + B细胞亚群的比例。此外，BAFF，APRIL，BAFFR，TACI和AID的表达减少，以及在BALF中的CD 11b + BAFF +细胞亚群的比例。总之，GBFXD对肺巨噬细胞分泌BAFF和BAFF相关受体的表达具有抑制作用，从而减少B细胞活化和IgE的释放。这一机制有助于改善哮喘小鼠模型的过敏性气道炎症和呼吸功能。
Allergic airway inflammation is one of the major pathological events involved in the development of asthma. The B cell-activating factor (BAFF)-mediated abnormal activation of B cells plays a key role in developing allergic airway inflammation. Here, we investigated the effects of Gu-Ben-Fang-Xiao decoction (GBFXD), a TCM decoction used in the prevention and treatment of allergic asthma, on allergic airway inflammation and BAFF-mediated B cell activation. A mouse model of OVA-Severe respiratory syncytial virus (RSV) induced asthma in the remission stage was administrated with GBFXD by gavage for four weeks, after which, the pulmonary function was evaluated. Pathological changes of the lung were observed by hematoxylin and eosin (HE) staining, and serum levels of IgE, BAFF, and inflammatory factors were detected by ELISA. The expression of BAFF, APRIL, and their related receptors in the lung and spleen was detected by Western blotting and RT-qPCR. Flow cytometry detected B cell subsets in the spleen, PBC, and monocyte subsets in bronchoalveolar lavage fluid (BALF). The results showed that GBFXD improved the lung function, alleviated the inflammatory changes of the lung tissue in OVA-RSV sensitized mice, and reduced levels of IL-6, TNF-alpha, IL1-beta, INOS, IL13 as well as IL-15, IgE, BAFF in the serum of OVA-RAV mice. Additionally, GBFXD significantly reduced the proportion of CD19+CD27+ B cell subpopulation and IgE + B cell subpopulation in the PBC and spleen cells of mice. Furthermore, the expression of BAFF, APRIL, BAFFR, TACI, and AID decreased in the lung and spleen of GBFXD-treated mice, as well as the proportion of CD11b + BAFF + cell subsets in BALF. In conclusion, GBFXD has an inhibitory effect on the secretion of BAFF by pulmonary macrophages and the expression of BAFF-related receptors, thereby reducing B cell activation and the release of IgE. This proposed mechanism contributes to the improvement of allergic airway inflammation and respiratory function in an asthmatic mouse model.