Lee Kijeong, Byun Junhyoung, Kim Byoungjae, Yeon Jiwoo, Tai Junhu, Lee Sang Hag, Kim Tae Hoon
Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul, Korea.
Neuroscience Research Institute, College of Medicine, Korea University, Seoul, Korea.
Am J Rhinol Allergy. 2021 Jul;35(4):432-440. doi: 10.1177/1945892420964169. Epub 2020 Oct 4.
Epithelial barrier disruption is a crucial feature of allergic rhinitis (AR). Previous reports have indicated the role of transient receptor potential vanilloid (TRPV) 4 in regulating the intercellular junctions in various cells. However, the role of TRPV4 and its regulation by T helper 2 cell cytokines in the epithelial cells of patients with AR remains unclear.
We aimed to elucidate the expression of TRPV4 in nasal epithelial cells and its cytokine-induced regulation, and to reveal its role in house dust mite-induced junction disruption in AR.
The expression of TRPV4 in nasal epithelial cells was measured using real-time polymerase chain reaction, western blot, and immunohistochemical assays, and the expression levels were compared between the patients with AR and healthy controls. Altered expression of TRPV4 was induced in cultured nasal epithelial cells by stimulation of interleukin (IL) 4, IL-13, and tumor necrosis factor alpha. In addition, expression of E-cadherin and zonula occludens 1 was induced in Der p 1-stimulated epithelial cells by treatment with either a TRPV4 agonist (GSK1016790A) or a TRPV4 antagonist (RN1734).
TRPV4 expression was increased in epithelial cells harvested from the affected turbinates compared to those from the normal turbinates. The stimulation of cultured epithelial cells with IL-4 and IL-13 resulted in TRPV4 upregulation. Additionally, E-cadherin and zonula occludens 1 expression levels decreased in the cultured epithelial cells treated with GSK1016790A after stimulation with Der p 1, whereas Der p 1 stimulation alone showed no effect on junctional protein expression.
Increased TRPV4 expression occurred in epithelial cells harvested from patients with AR and epithelial cells stimulated by Th2 cytokines. Decreased junctional protein expression in epithelial cells after the stimulation by house dust mite allergen with TRPV4 agonist indicates a possible role of TRPV4 in the pathogenesis of allergen-induced epithelial barrier disruption in AR.
上皮屏障破坏是变应性鼻炎（AR）的一个关键特征。既往报道表明，瞬时受体电位香草酸亚型4（TRPV4）在调节多种细胞的细胞间连接中发挥作用。然而，TRPV4在AR患者上皮细胞中的作用及其受辅助性T细胞2细胞因子的调控仍不清楚。
我们旨在阐明TRPV4在鼻上皮细胞中的表达及其细胞因子诱导的调控，并揭示其在屋尘螨诱导的AR交界破坏中的作用。
采用实时聚合酶链反应、蛋白质免疫印迹和免疫组织化学分析检测鼻上皮细胞中TRPV4的表达，并比较AR患者和健康对照者的表达水平。通过白细胞介素（IL）-4、IL-13和肿瘤坏死因子α刺激，在培养的鼻上皮细胞中诱导TRPV4表达改变。此外，用TRPV4激动剂（GSK1016790A）或TRPV4拮抗剂（RN1734）处理，在Der p 1刺激的上皮细胞中诱导E-钙黏蛋白和紧密连接蛋白1的表达。
与正常鼻甲上皮细胞相比，从患侧鼻甲采集的上皮细胞中TRPV4表达增加。用IL-4和IL-13刺激培养的上皮细胞导致TRPV4上调。此外，在用GSK1016790A处理的培养上皮细胞中，Der p 1刺激后E-钙黏蛋白和紧密连接蛋白1表达水平降低，而单独的Der p 1刺激对连接蛋白表达无影响。
在AR患者采集的上皮细胞和受Th2细胞因子刺激的上皮细胞中，TRPV4表达增加。屋尘螨变应原与TRPV4激动剂刺激后上皮细胞连接蛋白表达降低，表明TRPV4在变应原诱导的AR上皮屏障破坏发病机制中可能发挥作用。
