Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China; Otolaryngological Institute, Shanghai Jiao Tong University, Shanghai, PR China; Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, PR China.
Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China; Otolaryngological Institute, Shanghai Jiao Tong University, Shanghai, PR China; Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, PR China.
Int Immunopharmacol. 2021 Apr;93:107400. doi: 10.1016/j.intimp.2021.107400. Epub 2021 Jan 30.
RGFP966 is a selective inhibitor of histone deacetylase 3 (HDAC3) playing crucial roles in triggering allergic and inflammatory responses. Whereas, its role in allergic rhinitis (AR) remains uncertain. This study sought to illustrate the role and mechanism of HDAC3 inhibitor RGFP966 on allergic and inflammatory responses in murine AR. RGFP966 administration was applied on murine AR. HE staining, PAS staining, toluidine blue staining, immunohistochemistry staining and real-time PCR methods were used to assess eosinophils, goblet cells, mast cells, HDAC3 positive cells and mRNA levels in nasal tissues of mice. HDAC3 activities in nasal tissues were quantified with HDAC3 Activity Assay Kit. We collected blood and nasal lavage fluid (NLF) of mice for assaying IgE, inflammatory cytokines and inflammatory cells. Results indicated that RGFP966 intervention attenuated sneezing, nose rubbing, IgE, inflammatory cytokines, eosinophils, goblet cells, mast cells, inflammatory cells, HDAC3 levles and activities in RGFP966 treated mice. In conclusion, RGFP966 might reduce HDAC3 expression and HDAC3 activities, and then eosinophils and mast cells recruitment, goblet cells proliferation and inflammatory cytokines levels are decreased, resulting in the alleviation of allergic and inflammatory responses in AR mice.
RGFP966 是一种组蛋白去乙酰化酶 3（HDAC3）的选择性抑制剂，在引发过敏和炎症反应中起着至关重要的作用。然而，其在过敏性鼻炎（AR）中的作用尚不确定。本研究旨在阐明 HDAC3 抑制剂 RGFP966 在 AR 小鼠过敏和炎症反应中的作用和机制。对 AR 小鼠应用 RGFP966 进行干预。采用 HE 染色、PAS 染色、甲苯胺蓝染色、免疫组织化学染色和实时 PCR 方法评估小鼠鼻组织中的嗜酸性粒细胞、杯状细胞、肥大细胞、HDAC3 阳性细胞和 mRNA 水平。采用 HDAC3 活性检测试剂盒定量检测鼻组织中的 HDAC3 活性。收集小鼠血液和鼻洗液（NLF），用于检测 IgE、炎症细胞因子和炎症细胞。结果表明，RGFP966 干预可减轻 AR 小鼠的打喷嚏、鼻擦、IgE、炎症细胞因子、嗜酸性粒细胞、杯状细胞、肥大细胞、炎症细胞、HDAC3 水平和活性。综上所述，RGFP966 可能通过降低 HDAC3 的表达和活性，减少嗜酸性粒细胞和肥大细胞的募集、杯状细胞的增殖和炎症细胞因子的水平，从而缓解 AR 小鼠的过敏和炎症反应。
