title: Biphasic late airway hyperresponsiveness in a murine model of asthma.
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.
  
  
  CONCLUSIONS
  Biphasic late AHR occurs in a murine model of asthma. First- and second-phase late AHR is caused by TNF and Th2 response, respectively.
authors.affiliation: Department of Immunology, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Hae-Kyoung
authors.initials: HK
authors.lastname: Kim
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Lee
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Kim
authors.forename: Otgonzaya
authors.initials: O
authors.lastname: Ayush
authors.forename: Suhn-Yong
authors.initials: SY
authors.lastname: Im
authors.forename: Hern-Ku
authors.initials: HK
authors.lastname: Lee
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000503:physiopathology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015151:Immunoblotting; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000485:Allergens; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D010047:Ovalbumin