Role of STAT6 and SMAD2 in a model of chronic allergen exposure: a mouse strain comparison study.
Clin Exp Allergy
; 39(1): 147-58, 2009 Jan.
Article
en En
| MEDLINE
| ID: mdl-19032363
ABSTRACT
BACKGROUND:
Asthma is a disease characterized by variable and reversible airway obstruction and is associated with airway inflammation, airway remodelling (including goblet cell hyperplasia, increased collagen deposition and increased smooth muscle mass) and increased airway responsiveness. It is believed that airway inflammation plays a critical role in the development of airway remodelling, with IL-13 and TGF-beta1 pathways being strongly associated with the disease progression. Mouse models of asthma are capable of recapitulating some components of asthma and have been used to look at both IL-13 and TGF-beta1 pathways, which use STAT6 and SMAD2 signalling molecules, respectively.OBJECTIVES:
Using brief and chronic models of allergen exposure, we utilized BALB/c and C57Bl/6 to explore the hypothesis that observed differences in responses to allergen between these mouse strains will involve fundamental differences in IL-13 and TGF-beta1 responses.METHODS:
The following outcome measurements were performed airway physiology, bronchoalveolar lavage cell counts/cytokine analysis, histology, immunoblots and gene expression assays.RESULTS:
We demonstrate in BALB/c mice an IL-13-dependent phosphorylation of STAT6, nuclear localized in inflammatory cells, which is associated with indices of airway remodelling and development of airway dysfunction. In BALB/c mice, phosphorylation of SMAD2 is delayed relative to STAT6 activation and also involves an IL-13-dependent mechanism. In contrast, despite an allergen-induced increase in IL-4, IL-13 and eosinophils, C57Bl/6 demonstrates a reduced and distinct pattern of phosphorylated STAT6, no SMAD2 phosphorylation changes and fail to develop indices of remodelling or changes in airway function.CONCLUSION:
The activation of signalling pathways and nuclear translocation of signalling molecules downstream of IL-13 and TGF-beta1 further support the central role of these molecules in the pathology and dysfunction in animal models of asthma. Activation of signalling pathways downstream from IL-13 and TGF-beta1 may be more relevant in disease progression than elevations in airway inflammation alone.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Asma
/
Alérgenos
/
Modelos Animales de Enfermedad
/
Proteína Smad2
/
Factor de Transcripción STAT6
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Clin Exp Allergy
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Canadá