Background

Growing evidence shows that enhancer of zeste homolog 2 (EZH2) plays a role in various physiological functions and cancer pathogenesis. However, its contribution to allergic diseases remains controversial. We sought to investigate the role of EZH2 in the pathogenesis of allergic airway inflammation.

Methods

3-Deazaneplanocin A (DZNep), an indirect inhibitor of EZH2, was administered via intraperitoneal injection in an ovalbumin (OVA)-induced murine model of allergic airway inflammation. The expression of EZH2 in the allergic airway tissues was examined by immunohistochemistry (IHC) and western blot. The inflammatory cell infiltration and the goblet cell hyperplasia in the murine nose and lung were detected by hematoxylin and eosin (H&E) staining and periodic acid-Schiff (PAS) staining. Levels of cytokines, including IL-4, IFN-γ, IL-6, and IL-10, were evaluated in the bronchoalveolar lavage fluid (BALF) using Enzyme-linked immune sorbent assay (ELISA).

Results

EZH2 expression was inhibited by DZNep treatment (P < 0.05). The administration of DZNep significantly inhibited the inflammatory cell infiltration (P < 0.0001) and goblet cell hyperplasia (P < 0.001). Moreover, it suppressed the secretion of IL-4 (P < 0.0001) and IL-6 (P < 0.01) in the BALF.

Conclusions

Our findings demonstrate that DZNep attenuates allergic airway inflammation and could be a new therapeutic option for allergic rhinitis and asthma.

中文翻译：

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DZNep减轻卵清蛋白诱导的小鼠模型中的过敏性气道炎症

背景

越来越多的证据表明，zeste同系物2（EZH2）的增强子在各种生理功能和癌症发病机理中起作用。然而，其对过敏性疾病的贡献仍存在争议。我们试图研究EZH2在过敏性气道炎症的发病机理中的作用。

方法

通过卵白蛋白（OVA）诱导的小鼠过敏性气道炎症模型经腹膜内注射施用EZH2的间接抑制剂3-Deazaneplanocin A（DZNep）。通过免疫组织化学（IHC）和蛋白质印迹法检查过敏性气道组织中EZH2的表达。通过苏木精和曙红（H＆E）染色和高碘酸席夫（PAS）染色检测鼠鼻和肺中炎性细胞浸润和杯状细胞增生。使用酶联免疫吸附测定（ELISA）在支气管肺泡灌洗液（BALF）中评估了包括IL-4，IFN-γ，IL-6和IL-10在内的细胞因子水平。

结果

EZH2表达被DZNep处理所抑制（P <0.05）。DZNep的给药显着抑制了炎症细胞浸润（P <0.0001）和杯状细胞增生（P <0.001）。而且，它抑制了BALF中IL-4（P ＜0.0001）和IL-6（P ＜0.01）的分泌。

结论

我们的发现表明，DZNep可减轻过敏性气道炎症，并可能成为过敏性鼻炎和哮喘的新治疗选择。