Department of Otolaryngology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China; Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, China.
Department of Otolaryngology, Affiliated Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Mol Immunol. 2021 Mar;131:60-67. doi: 10.1016/j.molimm.2020.12.011. Epub 2020 Dec 25.
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.
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).
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.
Our findings demonstrate that DZNep attenuates allergic airway inflammation and could be a new therapeutic option for allergic rhinitis and asthma.
越来越多的证据表明，增强子结合蛋白 2（EZH2）在各种生理功能和癌症发病机制中发挥作用。然而，它在过敏性疾病中的作用仍存在争议。我们试图研究 EZH2 在过敏性气道炎症发病机制中的作用。
通过腹腔注射 3-去氮杂胞苷（DZNep），一种 EZH2 的间接抑制剂，在卵清蛋白（OVA）诱导的过敏性气道炎症小鼠模型中进行处理。通过免疫组织化学（IHC）和 Western blot 检测过敏性气道组织中 EZH2 的表达。通过苏木精和伊红（H&E）染色和过碘酸-Schiff（PAS）染色检测小鼠鼻和肺中的炎症细胞浸润和杯状细胞增生。通过酶联免疫吸附试验（ELISA）评估支气管肺泡灌洗液（BALF）中细胞因子，包括白细胞介素 4（IL-4）、干扰素 γ（IFN-γ）、白细胞介素 6（IL-6）和白细胞介素 10（IL-10）的水平。
DZNep 处理抑制了 EZH2 的表达（P < 0.05）。DZNep 给药显著抑制了炎症细胞浸润（P < 0.0001）和杯状细胞增生（P < 0.001）。此外，它抑制了 BALF 中 IL-4（P < 0.0001）和 IL-6（P < 0.01）的分泌。
我们的研究结果表明，DZNep 可减轻过敏性气道炎症，为变应性鼻炎和哮喘提供了新的治疗选择。
