Department of Otorhinolaryngology-Head and Neck Surgery, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Department of Medical Science, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Am J Rhinol Allergy. 2021 Nov;35(6):817-829. doi: 10.1177/19458924211004006. Epub 2021 Mar 18.
Exposure to airborne urban particulate matter (UPM) has been closely related to the development and aggravation of respiratory disease, including sinonasal disorders.
The aims of this study were to investigate the effect of UPM on nasal epithelial tight junctions (TJs) and mucosal barrier function and delineate the underlying mechanism by using both in vitro and in vivo models.
In this study, human nasal epithelial cells (hNECs) and BALB/c mice were exposed to UPMs. UPM 1648a and 1649 b were employed. TJ and endoplasmic reticulum (ER) stress marker expression was measured using western blot analysis and immunofluorescence. TJ integrity and nasal epithelial barrier function were evaluated by transepithelial electric resistance (TER) and paracellular flux. In addition, the effects of N-acetyl-L-cysteine (NAC) on UPM-induced nasal epithelial cells were investigated.
UPM significantly impaired the nasal epithelial barrier, as demonstrated by decreased protein expression of TJ and ER stress markers in human nasal epithelial cells. This finding was in parallel to reduced transepithelial electrical resistance and increased fluorescein isothiocyanate-dextran permeability. Pretreatment with NAC decreased the degree of UPM-mediated ER stress and restored nasal epithelial barrier disruption in human nasal epithelial cells (hNEC) and the nasal mucosa of experimental animals.
These data suggest that UPMs may induce nasal epithelial barrier dysfunction by targeting TJs and ER stress could be related in this process. Based on these results, we suggest that suppression of this process with an inhibitor targeting ER stress responses could represent a novel promising therapeutic target in UPM-induced sinonasal disease.
空气中的城市颗粒物（UPM）的暴露与呼吸道疾病的发展和恶化密切相关，包括鼻-鼻窦疾病。
本研究旨在通过体外和体内模型来研究 UPM 对鼻上皮紧密连接（TJ）和黏膜屏障功能的影响，并阐明其潜在机制。
在这项研究中，用人鼻上皮细胞（hNEC）和 BALB/c 小鼠暴露于 UPM。使用 UPM1648a 和 1649b。通过 Western blot 分析和免疫荧光法测量 TJ 和内质网（ER）应激标志物的表达。通过跨上皮电阻（TER）和旁细胞通量评估 TJ 完整性和鼻上皮屏障功能。此外，还研究了 N-乙酰-L-半胱氨酸（NAC）对 UPM 诱导的鼻上皮细胞的影响。
UPM 显著损害了鼻上皮屏障，这表现为 TJ 和 ER 应激标志物在人鼻上皮细胞中的蛋白表达降低。这一发现与跨上皮电阻降低和荧光素异硫氰酸酯-葡聚糖通透性增加平行。NAC 预处理可降低 UPM 介导的 ER 应激程度，并恢复人鼻上皮细胞（hNEC）和实验动物鼻黏膜中鼻上皮屏障的破坏。
这些数据表明，UPM 可能通过靶向 TJ 诱导鼻上皮屏障功能障碍，而 ER 应激可能与此过程有关。基于这些结果，我们建议用靶向 ER 应激反应的抑制剂抑制该过程可能是 UPM 诱导的鼻-鼻窦疾病的一个有前途的新治疗靶点。
