尘螨引起的过敏性鼻炎患者的屏障功能受损伴随着occludin和zonula occludens-1表达的降低
2016/06/20
摘要
背景：最近发现紧密连接（TJ）缺陷与哮喘和慢性鼻窦炎有关。过敏性鼻炎患者（AR）鼻黏膜上皮细胞紧密连接 的表达、功能和调控仍未可知。
目的：我们研究了屋尘螨引起(HDM)的过敏性鼻炎患者(AR)和屋尘螨诱导的过敏性气道病的小鼠模型的鼻黏膜上皮细胞紧密连接的表达、功能和调控。
方法：气液界面培养对照组和HDM诱导AR患者组的原代鼻腔上皮细胞，用于检测跨膜电阻和异硫氰酸荧光素-葡聚糖4kDa(FD4)的通道。测量鼻粘膜外植体的体外跨组织阻抗和FD4的通透性。采用实时定量PCR和免疫荧光测定紧密连接（TJ）的表达。此外，IL-4、IFN-γ，和丙酸氟替卡松（FP）对鼻粘膜上皮细胞的影响也做了体外研究。屋尘螨引起的过敏性小鼠模型被用来研究过敏性炎症和FP治疗对FD4体内跨膜通道的影响。
结果：在屋尘螨引起的过敏性鼻炎患者中，体外的阻抗降低，FD4的通透性增加，occudin和zonula occludens-1的表达降低。AR症状与HDM引起的AR患者的阻抗呈负相关。体外IL-4降低跨膜电阻、增加FD4的通透性，然而IFN-γ对它们不起作用。丙酸氟替卡松（FP）预防了体外IL-4诱导的屏障功能障碍。在HDM小鼠模型中，FP预防了过敏原诱导的黏膜通透性增加。
结论：我们发现在尘螨引起的过敏性鼻炎患者中存在鼻粘膜上皮屏障功能受损，伴有occludin and zonula occludens-1 表达更低。IL-4体外可破坏上皮细胞的完整性，FP可恢复屏障功能。更好地了解鼻腔屏障的调控可能会有助于了解过敏性鼻炎及其治疗。
（杨冬 审校）
JAllergyClinImmunol. 2016 Apr;137(4):1043-1053.e5.doi:10.1016/j.jaci.2015.10.050. Epub 2016 Feb 2.
Impaired barrier function in patients with house dust mite-induced allergic rhinitis is accompanied by decreased occludin and zonula occludens-1 expression.
Steelant B1, Farré R2, Wawrzyniak P3, Belmans J4, Dekimpe E5, Vanheel H2, Van Gerven L5, Kortekaas Krohn I1, Bullens DM4, Ceuppens JL1, Akdis CA3,Boeckxstaens G2, Seys SF1, Hellings PW6.
Author information
Abstract
BACKGROUND:Tight junction (TJ) defects have recently been associated with asthma and chronic rhinosinusitis. The expression, function, and regulation of nasal epithelial TJs remain unknown in patients with allergic rhinitis (AR).
OBJECTIVE:We investigated the expression, function, and regulation of TJs in the nasal epithelium of patients with house dust mite (HDM)-induced AR and in an HDM-induced murine model of allergic airway disease.
METHODS:Air-liquid interface cultures of primary nasal epithelial cells of control subjects and patients with HDM-induced AR were used for measuring transepithelial resistance and passage to fluorescein isothiocyanate-dextran 4 kDa (FD4). Ex vivo transtissue resistance and FD4 permeability of nasal mucosal explants were measured. TJ expression was evaluated by using real-time quantitative PCR and immunofluorescence. In addition, the effects of IL-4, IFN-γ, and fluticasone propionate (FP) on nasal epithelial cells were investigated in vitro. An HDM murine model was used to study the effects of allergic inflammation and FP treatment on transmucosal passage of FD4 in vivo.
RESULTS:A decreased resistance in vitro and ex vivo was found in patients with HDM-induced AR, with increased FD4 permeability and reduced occludin and zonula occludens-1 expression. AR symptoms correlated inversely with resistance in patients with HDM-induced AR. In vitro IL-4 decreased transepithelial resistance and increased FD4 permeability, whereas IFN-γ had no effect. FP prevented IL-4-induced barrier dysfunction in vitro. In an HDM murine model FP prevented the allergen-induced increased mucosal permeability.
CONCLUSION:We found impaired nasal epithelial barrier function in patients with HDM-induced AR, with lower occludin and zonula occludens-1 expression. IL-4 disrupted epithelial integrity in vitro, and FP restored barrier function. Better understanding of nasal barrier regulation might lead to a better understanding and treatment of AR.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
KEYWORDS:Allergic rhinitis; IL-4; epithelial permeability; epithelial resistance; fluticasone propionate; leak pathway; tight junctions
JAllergyClinImmunol. 2016 Apr;137(4):1043-1053.e5.doi:10.1016/j.jaci.2015.10.050. Epub 2016 Feb 2.
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