Xue Lingna, Li Cui, Ge Guangbo, Zhang Shaoyan, Tian Liming, Wang Yu, Zhang Huiyong, Ma Zifeng, Lu Zhenhui
Institute of Respiratory Disease, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Pharmacol. 2021 Jul 9;12:703724. doi: 10.3389/fphar.2021.703724. eCollection 2021.
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 . 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 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.
近几十年来，哮喘的发病率有所上升。尽管皮质类固醇和支气管扩张剂在临床实践中被使用，但哮喘的控制仍然是一项挑战。过敏性哮喘的特征是由2型免疫反应介导的气道炎症。2型固有淋巴细胞（ILC2s）是2型细胞因子IL-5和IL-13的重要来源，这两种细胞因子促进哮喘的进展。加味玉屏风散（JWYPFS）是一种中药，在中国已被广泛用于治疗哮喘。在本研究中，我们研究了JWYPFS治疗哮喘的机制，特别是对气道炎症中重要的ILC2s的影响。将雌性C57BL/6小鼠用卵清蛋白（OVA）致敏并激发，以建立过敏性哮喘模型。通过直接气道阻力分析检测气道高反应性。测定支气管肺泡灌洗液（BALF）中的炎性细胞计数。分别通过苏木精-伊红（HE）染色和过碘酸-雪夫（PAS）染色观察肺组织切片中的炎性细胞浸润和黏液分泌亢进情况。在肺组织样本中测量ILC2s的数量和比例以及与ILC2s相关的转录因子GATA3、IRF4和2型细胞因子。此外，从小鼠肺中收集ILC2s；在IL-33诱导ILC2s活化后，评估与ILC2s相关的细胞因子以及GATA3和IRF4。OVA处理的哮喘组中炎性细胞、黏液分泌、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治疗减轻了气道阻力，减少了包括嗜酸性粒细胞在内的炎性细胞，并抑制了这些哮喘小鼠的黏液产生和2型细胞因子。此外，JWYPFS治疗显著降低了ILC2s的数量和比例以及GATA3和IRF4的mRNA水平。在一项实验中，JWYPFS显著抑制了IL-33刺激的ILC2s中GATA3、IRF4和2型细胞因子的表达，包括IL-5和IL-13。JWYPFS减轻了ILC2s介导的气道炎症，表明JWYPFS可能是治疗过敏性哮喘的有效药物。
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