Protease-Activated Receptor-2 Decreased Zonula Occlidens-1 and Claudin-1 Expression and Induced Epithelial Barrier Dysfunction in Allergic Rhinitis
Jun Wang, Kang Xue, Zhi‐Qun Huang, Li Shen, Qing Luo, Mengyue Li, Liping Luo, Junhao Tu, Mei Han, Jing Ye
Abstract
BACKGROUND: Protease-activated receptor-2 (PAR-2)-modulated tight junctions (TJs) have been suggested to be involved in the pathogenesis of chronic inflammatory diseases. However, immunopathogenesis remains to be investigated among patients with allergic rhinitis (AR). OBJECTIVE: This study sought to investigate the role of PAR-2 in the modulation of epithelial barrier function and the expression of TJs in the nasal mucosa of AR patients. METHODS: , Primary human nasal epithelial cells (pHNECs) of AR patients were stimulated by Der p1 to analyze the correlation between PAR-2 and TJs expression. Der p1-induced pHNECs were treated with the PAR-2 agonist SLIGRL-NH2 and antagonist FSLLRY-NH2. Fluorescein isothiocyanate-dextran 4 kDa detection was employed as an indicator of epithelial permeability. RESULTS: Lower expression levels of TJs in the nasal epithelium of AR patients were observed in comparison with that in control subjects. The PAR-2 level was markedly increased following treatment with 1,000 ng/mL of Der p1 for 24 hours in a cellular model of AR. The expression of PAR-2 was increased in Der p1-induced pHNECs of AR patients and correlated inversely with zonula occlidens (ZO)-1 and claudin-1. Treatment with Der p1 further downregulated TJs expression and promoted an increased epithelial permeability in Der p1-induced pHNECs. CONCLUSIONS: PAR-2 could downregulate the expression of ZO-1 and claudin-1, which is involved in epithelial barrier dysfunction in AR.