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Clin Exp Allergy ; 45(9): 1447-58, 2015 Sep.
Article in English | 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.


Subject(s)
Asthma/immunology , Gene Expression Regulation/immunology , Goblet Cells/immunology , Interleukin-13/immunology , Lung/immunology , Signal Transduction/immunology , Animals , Asthma/metabolism , Asthma/pathology , Female , Forkhead Box Protein O3 , Forkhead Transcription Factors/biosynthesis , Forkhead Transcription Factors/immunology , Goblet Cells/metabolism , Goblet Cells/pathology , Interleukin-13/biosynthesis , Interleukin-13 Receptor alpha1 Subunit/biosynthesis , Interleukin-13 Receptor alpha1 Subunit/immunology , Interleukin-4/biosynthesis , Interleukin-4/immunology , Lung/metabolism , Lung/pathology , Metaplasia , Mice , Mice, Inbred BALB C , Mucus/immunology , Mucus/metabolism , Proto-Oncogene Proteins c-ets/biosynthesis , Proto-Oncogene Proteins c-ets/immunology , Th2 Cells/immunology , Th2 Cells/metabolism , Th2 Cells/pathology
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