Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon, 14584, Republic of Korea.
Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon, 14584, Republic of Korea.
Mol Immunol. 2021 Apr;132:209-216. doi: 10.1016/j.molimm.2021.01.004. Epub 2021 Jan 19.
Epithelial barrier dysfunction is involved in allergic inflammation and asthma, due to increased exposure of sub-epithelial tissues to inhaled allergens and air pollutants. The tight junction proteins claudins (CLDNs) are important regulators of paracellular permeability. CLDN7 is expressed in the alveolar epithelium; however, its contribution to airway barrier function remains unclear. The aim of this study was to assess the effects of TiO on epithelial barrier function in asthma. Mice were sensitized and challenged with OVA or exposed to TiO on days 21-23. The effect of TiO on CLDN7 was assessed by ELISA, immunoblotting, and immunohistochemical analysis. The levels of CLDN7 in the plasma of patients with asthma and healthy individuals were also examined. CLDN7 levels were lower in plasma from patients with asthma compared with healthy individuals. CLDN7 levels were associated with FEV/FVC and the blood eosinophils (%) in patients with asthma. Although CLDN7 expression was elevated in the lungs of mice with asthma and in NHBE cells treated with HDM extracts, its expression was suppressed by exposure to TiO. p-AKT and p-ERK was increased in asthmatic mice and decreased in mice with TiO treatment. p-AKT and p-ERK was decreased in NHBE cells treated with TiO and HDM extracts. Trans-epithelial electrical resistance (TEER) was higher in NHBE cells treated with TiO or HDM extracts; however, this was decreased by concurrent TiO and HDM extracts treatment. Our data suggest that particulate matter contributes to airway epithelial barrier dysfunction and results in airway inflammation and responsiveness.
上皮屏障功能障碍与过敏炎症和哮喘有关，这是由于上皮下组织暴露于吸入性过敏原和空气污染物增加所致。紧密连接蛋白 Claudins (CLDNs) 是细胞旁通透性的重要调节剂。CLDN7 在肺泡上皮细胞中表达，但它对气道屏障功能的贡献尚不清楚。本研究旨在评估 TiO 对哮喘中上皮屏障功能的影响。在第 21-23 天，用 OVA 对小鼠进行致敏和激发，或暴露于 TiO。通过 ELISA、免疫印迹和免疫组织化学分析评估 TiO 对 CLDN7 的影响。还检查了哮喘患者和健康个体血浆中 CLDN7 的水平。与健康个体相比，哮喘患者血浆中的 CLDN7 水平较低。CLDN7 水平与哮喘患者的 FEV/FVC 和血液嗜酸性粒细胞（%）相关。尽管哮喘小鼠肺中和用 HDM 提取物处理的 NHBE 细胞中 CLDN7 的表达升高，但 TiO 的暴露抑制了其表达。哮喘小鼠中的 p-AKT 和 p-ERK 增加，而 TiO 治疗的小鼠中则减少。用 TiO 和 HDM 提取物处理的 NHBE 细胞中的 p-AKT 和 p-ERK 减少。用 TiO 或 HDM 提取物处理的 NHBE 细胞中的跨上皮电阻 (TEER)较高，但同时用 TiO 和 HDM 提取物处理时则降低。我们的数据表明，颗粒物导致气道上皮屏障功能障碍，导致气道炎症和反应性。
