Zhou Xia, Dang Ya-Jie, Wang Gui-Fang, Jin Xian-Qiao
a Department of Respiratory Medicine , Huashan Hospital Affiliated to Fudan University , Shanghai , China.
b Department of Respiratory Medicine , Shanghai First People's Hospital Affiliated to Shanghai JiaoTong University , Shanghai , China.
Exp Lung Res. 2017 May-Jun;43(4-5):197-207. doi: 10.1080/01902148.2017.1339142. Epub 2017 Jul 11.
Conventional inhaled corticosteroids or β2-adrenergic receptor agonists do not work well in some asthmatic populations while empirical antifungal therapy has obvious impact on those patients. The study was designed to investigate whether short-term exposure to Aspergillus fumigatus (A. fumigatus) could decrease glucocorticoid receptor (GCR) and β2-adrenergic receptor (ADRB2) expression in lung tissue of asthmatic rats.
A rat model of chronic asthma was first established by ovalbumin sensitization and challenge. Rats with chronic asthma were then exposed to short-term application of A. fumigatus spores. Airway hyper-responsiveness, eosinophil ratio in bronchoalveolar lavage (BAL) fluid and total IgE in serum were counted in these experimental animals. GCR and ADRB2 expression in the lung were detected and analyzed. Furthermore, the levels of toll-like receptors (TLRs) 2, 3 and 4 in lung tissue were measured.
Short-term exposure to A. fumigatus could down-regulate the expression of GCR, aggravate airway hyper-responsiveness and increase the level of TLR2 in rats with asthma. There were no obvious changes in the levels of ADRB2 expression, recruited eosinophils, total IgE, TLR3 and TLR4 after application of A. fumigatus in asthmatic rats.
These findings indicate that A. fumigatus exposure may be involved in glucocorticoids unresponsiveness by down-regulating the expression of GCR in asthmatics. The possibility of A. fumigatus colonization or infection should not be ignored in patients of steroid-resistant asthma.
传统吸入性糖皮质激素或β2肾上腺素能受体激动剂在部分哮喘人群中效果不佳，而经验性抗真菌治疗对这些患者有明显影响。本研究旨在调查短期暴露于烟曲霉是否会降低哮喘大鼠肺组织中糖皮质激素受体（GCR）和β2肾上腺素能受体（ADRB2）的表达。
首先通过卵清蛋白致敏和激发建立大鼠慢性哮喘模型。然后将慢性哮喘大鼠短期暴露于烟曲霉菌孢子。对这些实验动物的气道高反应性、支气管肺泡灌洗（BAL）液中的嗜酸性粒细胞比例和血清总IgE进行计数。检测并分析肺组织中GCR和ADRB2的表达。此外，测量肺组织中Toll样受体（TLRs）2、3和4的水平。
短期暴露于烟曲霉可下调哮喘大鼠GCR的表达，加重气道高反应性，并增加TLR2水平。在哮喘大鼠应用烟曲霉后，ADRB2表达水平、募集的嗜酸性粒细胞、总IgE、TLR3和TLR4无明显变化。
这些发现表明，暴露于烟曲霉可能通过下调哮喘患者GCR的表达参与糖皮质激素无反应性。在激素抵抗性哮喘患者中，烟曲霉定植或感染的可能性不应被忽视。
