Jia-Wei-Yu-Ping-Feng-San Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation in Allergic Asthma.

Jia-Wei-Yu-Ping-Feng-San Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation in Allergic Asthma.
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加味玉屏风散减轻过敏性哮喘2型天然类风湿细胞介导的气道炎症

DOI:
10.3389/fphar.2021.703724
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发表时间:
2021
影响因子:
5.6
通讯作者:
Lu Z
Lu Z
中科院分区:
医学2区
文献类型:
--
作者:
Xue L;Li C;Ge G;Zhang S;Tian L;Wang Y;Zhang H;Ma Z;Lu Z

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近几十年来,哮喘的发病率有所增加。虽然皮质类固醇和支气管扩张剂在临床实践中使用,但哮喘的控制仍然是一个挑战。过敏性哮喘的特征是由2型免疫反应介导的气道炎症。第2组先天性淋巴样细胞(ILC 2)是2型细胞因子IL-5和IL-13的重要来源,其有助于哮喘的进展。加味玉屏风散是一种治疗哮喘的传统中药,在我国临床应用广泛。本研究旨在探讨加味养阴平喘方治疗哮喘的作用机制,尤其是对气道炎症中重要的ILC 2的影响。雌性C57 BL/6小鼠用卵清蛋白致敏并激发,建立过敏性哮喘模型。采用直接气道阻力分析法检测气道高反应性。测定支气管肺泡灌洗液(BALF)中的炎性细胞计数。肺组织切片HE染色可见炎性细胞浸润,PAS染色可见黏液高分泌。在肺组织样品中测量ILC 2以及ILC 2相关转录因子GATA 3、IRF 4和2型细胞因子的数量和比例。另外,从小鼠肺收集ILC 2;在IL-33体外诱导ILC 2活化后评价ILC 2相关细胞因子和GATA 3和IRF 4。OVA治疗组的炎症细胞、粘液分泌、气道高反应性和2型细胞因子升高,表明已建立过敏性哮喘模型。JWYPFS治疗减弱了这些哮喘小鼠的气道阻力,减少了包括嗜酸性粒细胞在内的炎性细胞,并抑制了粘液产生和2型细胞因子。此外,JWYPFS治疗显着降低ILC 2的数量和比例以及GATA 3和IRF 4的mRNA水平。在体外实验中,JWYPFS显著抑制GATA 3、IRF 4和2型细胞因子表达,包括IL-33刺激的ILC 2中的IL-5和IL-13。JWYPFS能抑制ILC 2s介导的气道炎症,提示JWYPFS可能是治疗过敏性哮喘的有效药物。
The incidence of asthma has increased in recent decades. Although corticosteroids and bronchodilators are used in clinical practice, the control of asthma remains a challenge. Allergic asthma is characterized airway inflammation mediated by type 2 immune response. Group 2 innate lymphoid cells (ILC2s) are an important source of type 2 cytokines IL-5 and IL-13, which contribute to the progress of asthma. Jia-Wei-Yu-Ping-Feng-San (JWYPFS), a traditional Chinese medicine, has been widely used to treat asthma in China. In this study we investigated the mechanisms of JWYPFS in the treatment of asthma, especially the effect on ILC2s important in airway inflammation. Female C57BL/6 mice were sensitized and challenged with OVA to establish a model of allergic asthma. Airway hyperresponsiveness was examined by direct airway resistance analysis. Inflammatory cell counts were determined in bronchoalveolar lavage fluid (BALF). Inflammatory cell infiltration and mucus hypersecretion in lung tissue sections was observed by HE and PAS staining, respectively. The numbers and proportions of ILC2s as well as the ILC2s-related transcription factors GATA3, IRF4, and type 2 cytokines were measured in lung tissue samples. Additionally, ILC2s were collected from mouse lung; ILC2s-related cytokines and GATA3 and IRF4 were evaluated after IL-33-induced activation of ILC2s in vitro. Elevated inflammatory cells, mucus secretion, airway hyperresponsiveness and type 2 cytokines in the OVA-treated asthma group indicated that an allergic asthma model had been established. JWYPFS treatment attenuated airway resistance and reduced inflammatory cells including eosinophils, and inhibited mucus production and type 2 cytokines in these asthmatic mice. Moreover, JWYPFS treatment dramatically decreased the numbers and proportions of ILC2s and the mRNA levels of GATA3 and IRF4. In an in vitro experiment JWYPFS significantly suppressed GATA3, IRF4 and type 2 cytokine expression, including IL-5 and IL-13 in IL-33-stimulated ILC2s. JWYPFS alleviates ILC2s-mediated airway inflammation, suggesting that JWYPFS might be an effective agent to treat allergic asthma.
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发表时间: 2010-04
期刊: Lung India : official organ of Indian Chest Society
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Deo SS;Mistry KJ;Kakade AM;Niphadkar PV
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