Ma Siyuan, Xian Mu, Wang Yang, Wang Chengshuo, Zhang Luo
Department of Otolaryngology Head and Neck Surgery Beijing TongRen Hospital Capital Medical University Beijing China.
Beijing Key Laboratory of Nasal Diseases Beijing Institute of Otolaryngology Beijing China.
Clin Transl Allergy. 2021 Jul 3;11(5):e12019. doi: 10.1002/clt2.12029. eCollection 2021 Jul.
Eosinophilic chronic rhinitis with nasal polyps (eos-CRSwNP) is a subtype of nasal polyps (NPs) characterized by severe type-2 inflammation and defective epithelial barrier function. The epithelial barrier plays important roles in the pathogenesis of NPs and type-2 inflammation. Particular matter 2.5 (PM) are fine particles with a diameter less than 2.5 μm, containing a mixture of different components. Here, we investigated the impact of PM on the barrier function of the eos-CRSwNP epithelium and explored the reparative function of budesonide.
Samples from noninflammatory nasal mucosa and eos-CRSwNP were collected to establish an in vitro air-liquid interface cultured model. The cells were exposed to PM at 50 or 100 µg/ml intermittently for 72 h, with or without budesonide pretreatment. Barrier function and tight junction (TJ) expression were reflected by measuring transepithelial resistance (TER), paracellular flux permeability of fluorescein isothiocyanate-labeled 4-kDa dextran, quantitative real-time polymerase chain reaction (qPCR), and immunofluorescence staining of TJ proteins. Cytokine expression was measured by qPCR and enzyme-linked immunosorbent assay or Luminex.
PM increased paracellular flux and downregulated TJ protein expression (zona occuldens-1, occludin, and claudin-1), but did not change TER. These changes could be partially restored by budesonide treatment. Interleukin (IL)-8, IL-10, IL-1, and tissue inhibitor of metalloproteinase (TIMP)-1 concentrations were significantly increased in the culture medium of cells exposed to PM, and budesonide significantly reduced the changes in IL-8, IL-1, and TIMP-1.
PM impaired the barrier function of eos-CRSwNP epithelial cells and increased the permeability of large molecules. PM also increased the secretion of pro-inflammatory cytokines by nasal epithelial cells. Budesonide could partially repair the damage, suggesting potential applications in clinical practice.
嗜酸性粒细胞性慢性鼻-鼻窦炎伴鼻息肉（eos-CRSwNP）是鼻息肉（NP）的一种亚型，其特征为严重的2型炎症和上皮屏障功能缺陷。上皮屏障在NP和2型炎症的发病机制中起重要作用。细颗粒物2.5（PM）是直径小于2.5μm的细颗粒，包含不同成分的混合物。在此，我们研究了PM对eos-CRSwNP上皮屏障功能的影响，并探讨了布地奈德的修复功能。
收集非炎性鼻黏膜和eos-CRSwNP的样本，建立体外气液界面培养模型。细胞间歇性暴露于50或100μg/ml的PM中72小时，有无布地奈德预处理。通过测量跨上皮电阻（TER）、异硫氰酸荧光素标记的4 kDa葡聚糖的细胞旁通量通透性、定量实时聚合酶链反应（qPCR）和紧密连接（TJ）蛋白的免疫荧光染色来反映屏障功能和TJ表达。通过qPCR、酶联免疫吸附测定或Luminex测量细胞因子表达。
PM增加了细胞旁通量并下调了TJ蛋白表达（闭合蛋白-1、闭合蛋白和紧密连接蛋白-1），但未改变TER。布地奈德治疗可部分恢复这些变化。暴露于PM的细胞培养基中白细胞介素（IL）-8、IL-
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