Abstract
Background: 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. Objective: 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. Methods: 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). Results: 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. Conclusions: 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.
| Original language | English |
|---|---|
| Pages (from-to) | 432-440 |
| Number of pages | 9 |
| Journal | American Journal of Rhinology and Allergy |
| Volume | 35 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2021 Jul |
Bibliographical note
Funding Information:We would like to thank Editage (www.editage.co.kr) for English language editing. The author(s) received the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Basic Science Research Program, National Research Foundation of Korea, funded by the Ministry of Science and Technology and the Ministry of Science, ICT & Future Planning (2017R1A2B2003575, NRF-2020R1A2C1006398), and the Korea Health Technology R&D Project (HI17C0387), Korea Health Industry Development Institute (KHIDI), and the Ministry of Health & Welfare. This research was also supported by a Korea University grant, and a grant from Korea University Medical Center as well as by Anam Hospital, Seoul, Republic of Korea (O1905011).
Publisher Copyright:
© The Author(s) 2020.
Keywords
- E-cadherin
- TRPV4
- ZO-1
- allergen
- allergic rhinitis
- cytokine
- epithelial barrier
- epithelial cells
- house dust mites
- transient receptor potential vanilloid channels
ASJC Scopus subject areas
- Immunology and Allergy
- Otorhinolaryngology