Abrogation of bronchial eosinophilic inflammation and airway hyperreactivity in signal transducers and activators of transcription (STAT)6-deficient mice.
Signal transducers and activators of transcription 6 (STAT6) is essential for interleukin 4-mediated responses, including class switching to IgE and induction of type 2 T helper cells. To investigate the role of STAT6 in allergic asthma in vivo, we developed a murine model of allergen-induced airway inflammation. Repeated exposure of actively immunized C57BL/6 mice to ovalbumin (OVA) aerosol increased the level of serum IgE, the number of eosinophils in bronchoalveolar lavage (BAL) fluid, and airway reactivity. Histological analysis revealed peribronchial inflammation with pulmonary eosinophilia in OVA-treated mice. In STAT6-deficient (STAT6-/-) C57BL/6 mice treated in the same fashion, there were no eosinophilia in BAL and significantly less peribronchial inflammation than in wild-type mice. Moreover STAT6-/- mice had much less airway reactivity than wild-type mice. These findings suggest that STAT6 plays a crucial role in the pathogenesis of allergen-induced airway inflammation.
Akimoto
T
T
New Product Research Laboratories IV, Daiichi Pharmaceutical Co., Ltd., 1-16-13 Kitakasai, Edogawa, Tokyo 134, Japan. jde03537@niftyserve.or.jp
Numata
F
F
Tamura
M
M
Takata
Y
Y
Higashida
N
N
Takashi
T
T
Takeda
K
K
Akira
S
S
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007249:Inflammation / Q000276:immunology*; D008168:Lung / Q000166:cytology / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000172:deficiency*
D007075:Immunoglobulin M; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D007073:Immunoglobulin E; D010047:Ovalbumin