Distal airways are protected from goblet cell metaplasia by diminished expression of IL-13 signalling components.
Clin Exp Allergy
; 45(9): 1447-58, 2015 Sep.
Article
en En
| MEDLINE
| ID: mdl-25772331
ABSTRACT
BACKGROUND:
Increased mucus production is a critical factor impairing lung function in patients suffering from bronchial asthma, the most common chronic inflammatory lung disease worldwide.OBJECTIVE:
This study aimed at investigating whether goblet cell (GC) metaplasia and mucus production are differentially regulated in proximal and distal airways.METHODS:
Female Balb/c mice were sensitized to ovalbumin (OVA) and challenged with an OVA-aerosol on two consecutive days for 1 week (acute) or 12 weeks (chronic). Real-time RT-PCR analysis was applied on microdissected airways.RESULTS:
In acutely and chronically OVA-challenged mice, GC metaplasia and mucus production were observed in proximal but not in distal airways. In contrast, inflammation reflected by the infiltration of eosinophils and expression of the TH2-type cytokines IL-4 and IL-13 was increased in both proximal and distal airways. Abundance of IL-13Rα1 was lower in distal airways of healthy control mice. Under acute and chronic OVA-exposure, activation of IL-13Rα1-dependent signalling cascade, reflected by Spdef and Foxo3A transcription factors, was attenuated in distal compared to proximal airways. CONCLUSION AND CLINICAL RELEVANCE These data indicate that distal airways might be less sensitive to IL-13-induced GC metaplasia and mucus production through lower expression of IL-13Rα1 and attenuated activation of downstream signalling. This might represent a protective strategy to prevent mucus plugging of distal airways and thus impaired ventilation of attached alveoli.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Asma
/
Transducción de Señal
/
Regulación de la Expresión Génica
/
Interleucina-13
/
Células Caliciformes
/
Pulmón
Límite:
Animals
Idioma:
En
Revista:
Clin Exp Allergy
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Alemania