BACKGROUND: Transcriptional factors of the signal transducer and activator of transcription (STAT) family play an important role in orchestrating immune reactions. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: Transcriptional factors of the signal transducer and activator of transcription (STAT) family play an important role in orchestrating immune reactions. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Guoping Li; John Fox; Zhigang Liu; Jun Liu; George F Gao; Yang Jin; Hongwei Gao; Min Wu Journal: J Immunol Date: 2013-10-14 Impact factor: 5.422
Authors: Wang-Jian Zha; Yan Qian; Yi Shen; Qiang Du; Fei-Fei Chen; Zhen-Zhen Wu; Xiao Li; Mao Huang Journal: Evid Based Complement Alternat Med Date: 2013-05-25 Impact factor: 2.629
Authors: Tomislav Stojanovic; Andreas H Wagner; Shijun Wang; Eva Kiss; Nicolas Rockstroh; Jens Bedke; Hermann-Josef Gröne; Markus Hecker Journal: Basic Res Cardiol Date: 2009-04-08 Impact factor: 17.165