Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Gyeonggi-Do, South Korea.
Clin Exp Allergy. 2013 Aug;43(8):914-27. doi: 10.1111/cea.12143.
Asthma is characterized by chronic airway inflammation triggered by various allergens in the environment. Defects in the bronchial epithelial interface with the external environment are the hallmark of asthma. Apolipoprotein A-1 (ApoA1) or ApoA1 mimetics have demonstrated anti-inflammatory activity and preventive effects in mouse models.
We investigated airway levels of ApoA1 in asthmatics and the possible role of ApoA1 in protection of the bronchial epithelium and in resolution of inflammation in cellular and animal models of asthma.
ApoA1 levels were measured in bronchoalveolar lavage fluid (BALF) from asthmatics and healthy controls. With treatment of ApoA1, mouse model of house dust mite (HDM)-driven asthma and cultured primary bronchial epithelial cells obtained from asthmatics were examined. Tight junction (TJ) expression in the bronchial epithelial cells was assessed by using confocal microscopy and immunoblot.
Asthmatics showed significantly lower ApoA1 levels in bronchoalveolar lavage fluid than did healthy controls. Local ApoA1 treatment significantly decreased lung IL-25, IL-33, and thymic stromal lymphopoietin levels in HDM-challenged mice and inhibited allergen-induced production of these cytokines in cultured primary bronchial epithelial cells. ApoA1 promoted recovery of disrupted TJ proteins zonula occludens-1 and occludin in cultured primary bronchial epithelium obtained from asthmatics. ApoA1-induced increases in the TJ proteins were dependent on increased production of lipoxin A4 (LX A4).
ApoA1 enhances resolution of allergen-induced airway inflammation through promoting recovery of damaged TJs in the bronchial epithelium. ApoA1 could be a therapeutic strategy in chronic airway inflammatory diseases that are associated with a defective epithelial barrier, including asthma.
哮喘的特征是由环境中的各种过敏原引发的慢性气道炎症。支气管上皮与外界环境的界面缺陷是哮喘的标志。载脂蛋白 A-1（ApoA1）或 ApoA1 模拟物已在小鼠模型中显示出抗炎活性和预防作用。
我们研究了哮喘患者气道中的 ApoA1 水平，以及 ApoA1 在保护支气管上皮和缓解哮喘细胞和动物模型中的炎症中的可能作用。
测量了哮喘患者和健康对照者支气管肺泡灌洗液（BALF）中的 ApoA1 水平。用 ApoA1 处理后，检查了屋尘螨（HDM）驱动的哮喘小鼠模型和从哮喘患者中获得的培养原代支气管上皮细胞。通过共聚焦显微镜和免疫印迹评估支气管上皮细胞中的紧密连接（TJ）表达。
哮喘患者的支气管肺泡灌洗液中的 ApoA1 水平明显低于健康对照组。局部 ApoA1 治疗显著降低了 HDM 挑战小鼠的肺白介素 25、白介素 33 和胸腺基质淋巴细胞生成素水平，并抑制了培养的原代支气管上皮细胞中这些细胞因子的产生。ApoA1 促进了从哮喘患者中获得的培养原代支气管上皮中破坏的 TJ 蛋白紧密连接蛋白-1 和闭合蛋白的恢复。ApoA1 诱导的 TJ 蛋白增加依赖于脂氧素 A4（LX A4）的增加。
ApoA1 通过促进支气管上皮受损 TJ 的恢复，增强了过敏原诱导的气道炎症的消退。ApoA1 可能是一种治疗策略，适用于与上皮屏障缺陷相关的慢性气道炎症性疾病，包括哮喘。
