Ravi Abilash, Chowdhury Saheli, Dijkhuis Annemiek, Dierdorp Barbara S, Dekker Tamara, Kruize Rianne, Sabogal Piñeros Yanaika S, Majoor Christof J, Sterk Peter J, Lutter René
Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Dept of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands.
ERJ Open Res. 2022 Apr 19;8(2). doi: 10.1183/23120541.00522-2021. eCollection 2022 Apr.
Defective translocation of the translational repressor TIAR (T-cell internal antigen receptor) in bronchial epithelial cells (BECs) from asthma patients underlies epithelial hyperresponsiveness, reflected by an exaggerated production of a select panel of inflammatory cytokines such as CXCL-8, interleukin (IL)-6, granulocyte colony-stimulating factor, CXCL-10, upon exposure to tumour necrosis factor (TNF) and IL-17A. With this study we aimed to clarify whether epithelial hyperresponsiveness is a consistent finding, is changed upon exposure to rhinovirus (RV)-A16 and applies to the bronchoconstrictor endothelin-1.
BECs were obtained from asthma patients (n=18) and healthy individuals (n=11), 1 day before and 6 days post-RV-A16 exposure. BECs were cultured and stimulated with TNF and IL-17A and inflammatory mediators were analysed. The bronchoalveolar lavage fluid (BALF) was obtained in parallel with BECs to correlate differential cell counts and inflammatory mediators with epithelial hyperresponsiveness.
Epithelial hyperresponsiveness was confirmed in sequential samples and even increased in BECs from asthma patients after RV-A16 exposure, but not in BECs from healthy individuals. Endothelin-1 tended to increase in BECs from asthma patients collected after RV-A16 exposure, but not in BECs from healthy individuals. CXCL-8 and endothelin-1 production correlated. relevance for CXCL-8 and endothelin-1 production was shown by correlations with forced expiratory volume in 1 s % predicted and CXCL-8 BALF levels.
Epithelial hyperresponsiveness is an intrinsic defect in BECs from asthma patients, which increases upon viral exposure, but not in BECs from healthy individuals. This epithelial hyperresponsiveness also applies to the bronchoconstrictor endothelin-1, which could be involved in airway obstruction.
哮喘患者支气管上皮细胞（BECs）中翻译抑制因子TIAR（T细胞内抗原受体）的转运缺陷是上皮高反应性的基础，这表现为在暴露于肿瘤坏死因子（TNF）和白细胞介素（IL）-17A后，一组特定的炎性细胞因子如CXCL-8、白细胞介素（IL）-6、粒细胞集落刺激因子、CXCL-10产生过量。通过本研究，我们旨在阐明上皮高反应性是否为一致的发现，在暴露于鼻病毒（RV）-A16后是否会改变，以及是否适用于支气管收缩剂内皮素-1。
在暴露于RV-A16前1天和暴露后6天，从哮喘患者（n = 18）和健康个体（n = 11）获取BECs。培养BECs并用TNF和IL-17A刺激，分析炎性介质。与BECs同时获取支气管肺泡灌洗液（BALF），以将不同细胞计数和炎性介质与上皮高反应性相关联。
在连续样本中证实了上皮高反应性，并且在暴露于RV-A16后，哮喘患者的BECs中上皮高反应性甚至增加，但健康个体的BECs中未增加。暴露于RV-A16后收集的哮喘患者的BECs中内皮素-1有增加趋势，但健康个体的BECs中未增加。CXCL-8和内皮素-1的产生相关。与1秒用力呼气量占预计值百分比和CXCL-8 BALF水平的相关性表明了CXCL-8和内皮素-1产生的相关性。
上皮高反应性是哮喘患者BECs的固有缺陷，在病毒暴露后会增加，但健康个体的BECs中不会增加。这种上皮高反应性也适用于支气管收缩剂内皮素-1，其可能参与气道阻塞。
