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Histone deacetylase activity is a novel target for epithelial barrier defects in patients with eosinophilic chronic rhinosinusitis with nasal polyps

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机构： [1]Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, China. [2]Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China. [3]Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China. [4]Research Unit of Diagnosis and Treatment of Chronic Nasal Disease, Chinese Academy of Medical Sciences, Beijing, China.

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关键词： eosinophilic chronic rhinosinusitis with nasal polyps epithelial barrier histone deacetylases noneosinophilic chronic rhinosinusitis with nasal polyps tight junctions

摘要：

Studies have independently indicated that eosinophils and histone deacetylases (HDACs) may compromise the integrity of the epithelial barrier in nasal polyps; however, the underlying mechanisms are not clear. In this study, we aimed to investigate the role of eosinophilia and HDACs in regulation of tight junctions (TJs) and nasal epithelial barrier integrity in chronic rhinosinusitis with nasal polyps (CRSwNP) patients.Expression of mRNAs and proteins of TJs and HDACs of biopsy specimens and air-liquid interface (ALI) human nasal epithelial cell cultures (HNECs) from eosinophilic and noneosinophilic CRSwNP patients and healthy controls was assessed. The ALI HNECs were also assessed for changes in transepithelial electrical resistance (TER) and paracellular flux of fluorescein isothiocyanate (FITC)-labelled dextran. Meanwhile, the assessments for the effect of HDAC inhibitor in eosinophilic nasal polyps were also conducted.Decreased TER and increased paracellular flux of FITC-labelled dextran in the ALI cultures were found in both eosinophilic and noneosinophilic CRSwNP, along with irregular, patchy and reduced expression of claudin-1, 4, 7, occludin, zonula occludens (ZO)-1 and ZO-2 and increased expression of HDAC1, 9 and SIRT7 for both ALI culture cells and biopsy specimens, especially for the eosinophilic CRSwNP group. Treatment of eosinophilic CRSwNP ALI-HNECs with an HDAC inhibitor improved the TJs expression and epithelial barrier integrity.Our data suggest that eosinophilia and HDACs influence epithelial barrier function in CRSwNP patients by regulating TJ protein expression. Targeting HDACs with specific inhibitors may be a potential treatment option for patients with eosinophilic CRSwNP.© 2022 John Wiley & Sons Ltd.

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出版当年[2022]版：

大类 | 2 区医学

小类 | 2 区免疫学 2 区过敏

最新[2025]版：

大类 | 2 区医学

小类 | 2 区过敏 2 区免疫学

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出版当年[2021]版：

Q2 ALLERGY Q2 IMMUNOLOGY

最新[2023]版：

Q1 ALLERGY Q1 IMMUNOLOGY

影响因子： 6.3 最新[2023版] 5.2 最新五年平均 5.401 出版当年[2021版] 5.597 出版当年五年平均 5.018 出版前一年[2020版] 6.1 出版后一年[2022版]

第一作者：

第一作者机构： [1]Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

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通讯作者：

通讯机构： [1]Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, China. [2]Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China. [3]Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China. [4]Research Unit of Diagnosis and Treatment of Chronic Nasal Disease, Chinese Academy of Medical Sciences, Beijing, China. [*1]Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Beijing Institute of Otolaryngology, Capital Medical University, No. 17, HouGouHuTong, DongCheng District, Beijing 100730, China.

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Histone deacetylase activity is a novel target for epithelial barrier defects in patients with eosinophilic chronic rhinosinusitis with nasal polyps

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