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- Title
Biphasic Late Airway Hyperresponsiveness in a Murine Model of Asthma.
- Authors
Kim, Hae-Kyoung; Lee, Chang-Hoon; Kim, Jun-Mo; ayush, Otgonzaya; Im, Suhn-Yong; Lee, Hern-Ku
- 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 B4 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
- Subjects
ASTHMA; AIRWAY (Anatomy); LABORATORY mice; MAST cells; TUMOR necrosis factors; INFLAMMATION
- Publication
International Archives of Allergy & Immunology, 2013, Vol 160, Issue 2, p173
- ISSN
1018-2438
- Publication type
Article
- DOI
10.1159/000341645