Quarcoo David, Weixler Silke, Groneberg David, Joachim Ricarda, Ahrens Birgit, Wagner Andreas H, Hecker Markus, Hamelmann Eckard
Department of Pediatric Pneumology and Immunology, Charité-Humboldt University, Berlin, Germany.
J Allergy Clin Immunol. 2004 Aug;114(2):288-95. doi: 10.1016/j.jaci.2004.03.055.
Transcriptional factors of the signal transducer and activator of transcription (STAT) family play an important role in orchestrating immune reactions.
The aim of the current study was to investigate the role of STAT-1 in murine allergen-induced sensitization and development of airway inflammation (AI) and airway hyperreactivity (AHR), cardinal features of bronchial asthma.
BALB/c mice were systemically sensitized to ovalbumin and challenged with ovalbumin through the airways. Decoy oligonucleotide (ODN) specific for STAT-1 was applied once locally to the airways of sensitized animals before allergen airway challenges.
Single application of decoy ODN markedly and significantly reduced numbers of eosinophils and lymphocytes in bronchoalveolar lavage fluids compared with those seen in sensitized and challenged animals receiving mutant control ODN. Associated with this decrease in eosinophilic AI were significantly reduced levels of IL-5 in BAL fluid, of CD40 expression in peribronchial infiltrates, and of vascular cell adhesion molecule 1 expression in vascular endothelial cells, respectively. In addition, development of AHR after allergen sensitization and airway challenges was effectively abolished after local STAT-1 decoy ODN treatment.
The data indicate that a decoy ODN neutralizing STAT-1 effectively inhibits allergen-induced AI and AHR, probably by attenuating upregulation of costimulatory and adhesion molecules, and suggest a significant role of STAT-1 in asthma pathology.
信号转导子与转录激活子（STAT）家族的转录因子在协调免疫反应中发挥重要作用。
本研究旨在探讨STAT-1在小鼠变应原诱导的致敏以及气道炎症（AI）和气道高反应性（AHR）（支气管哮喘的主要特征）发展过程中的作用。
将BALB/c小鼠对卵清蛋白进行全身致敏，然后通过气道给予卵清蛋白激发。在变应原气道激发前，将针对STAT-1的诱饵寡核苷酸（ODN）局部应用于致敏动物的气道一次。
与接受突变对照ODN的致敏和激发动物相比，单次应用诱饵ODN可显著降低支气管肺泡灌洗液中嗜酸性粒细胞和淋巴细胞的数量。与嗜酸性粒细胞性AI的减少相关，BAL液中IL-5水平、支气管周围浸润中CD40表达以及血管内皮细胞中血管细胞黏附分子1表达分别显著降低。此外，局部STAT-1诱饵ODN处理后，变应原致敏和气道激发后AHR的发展被有效消除。
数据表明，中和STAT-1的诱饵ODN可能通过减弱共刺激分子和黏附分子的上调，有效抑制变应原诱导的AI和AHR，并提示STAT-1在哮喘病理过程中起重要作用。
