151. Biphasic late airway hyperresponsiveness in a murine model of asthma.
- Author
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Kim HK, Lee CH, Kim JM, Ayush O, Im SY, and Lee HK
- Subjects
- Allergens immunology, Animals, Asthma physiopathology, Bronchial Hyperreactivity physiopathology, Cytokines immunology, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Female, Immunoblotting, Inflammation immunology, Inflammation physiopathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Ovalbumin immunology, Th2 Cells immunology, Tumor Necrosis Factor-alpha immunology, Asthma immunology, Bronchial Hyperreactivity immunology
- Abstract
Background: Nonspecific airway hyperresponsiveness (AHR) is one of the cardinal features of bronchial asthma. Early AHR is caused by chemical mediators released from pulmonary mast cells activated in an IgE-dependent way. However, the mechanism of late AHR remains unclear., Methods: Features of airway allergic inflammation were analyzed, including antigen-induced AHR, using a murine model of asthma. The model was suitable for examining the sequential early molecular events occurring after the initial airway exposure to antigen., Results: AHR increased at 10-12 h after airway challenge, followed by the second-phase response, which was larger and broader in resistance at 18-30 h. Pretreatment of sensitized animals with anti-tumor necrosis factor (TNF) before airway challenge or induction of allergic asthma in TNF(-/-) mice resulted in abrogation of the first-phase late AHR. Intratracheal instillation of TNF induced a single peak of AHR at 10 h. IgE and IgG immune complexes induced the development of the first-phase late AHR by TNF production. Pretreatment with cytosolic phospholipase inhibitor and 5-lipoxygenase inhibitors abolished the first-phase late AHR as well as the leukotriene B(4) levels in the airway. CpG-oligodeoxynucleotide (ODN) pretreatment reduced airway levels of Th2 cytokines, eosinophil infiltration and second-phase late AHR. However, CpG-ODN did not reduce TNF levels or the magnitude of first-phase late AHR., Conclusion: Biphasic late AHR occurs in a murine model of asthma. First- and second-phase late AHR is caused by TNF and Th2 response, respectively., (Copyright © 2012 S. Karger AG, Basel.)
- Published
- 2013
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