Pneumologie 2012; 66 - A206
DOI: 10.1055/s-0032-1315472

Region-specific regulation of mucus production in allergic asthma is dependent on IL-13R alpha 1 expression

C Vock 1, AÖ Yildirim 2, M Wegmann 1, H Fehrenbach 1
  • 1Section of Experimental Pneumology, Research Center Borstel, Airway Research Centre North, Member of the German Center for Lung Research
  • 2Comprehensive Pneumology Center, Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum Munich

Increased mucus production is a critical factor impairing lung function in patients suffering from bronchial asthma, the most common chronic inflammatory disease worldwide.

In acute and chronic mouse models of allergic asthma metaplasia of mucus producing goblet cells (GC) was found in proximal but not in distal airways although secretion of interleukin (IL)-13, the main trigger of mucus production, was significantly elevated along the entire airway tree. The current study aimed at elucidating what detains TH2 cell derived IL-13 from inducing GC metaplasia in distal airways by investigating the IL-13 signalling cascade.

BALB/c mice were sensitized with OVA/Alum and subsequently challenged with OVA for one (acute) or twelve weeks (chronic). To assess lung morphology, lungs were fixed under constant pressure with 4% paraformaldehyde followed by paraffin embedding. Systematic uniform samples were stained with periodic acid Schiff (PAS) to analyse mucus production. Lungs were inflated with RNAlater® to microdissect proximal and distal airways for qRT-PCR.

Quantitative RT-PCR revealed higher expression of the IL-13Rα1in proximal airways in both acutely (1.5-fold) and chronically (1.5-fold) challenged mice as well as in PBS-treated control animals (1.3-fold). Expression levels of transcription factors down-stream the IL-13Rα1 signalling implicated in mucus hyper-production, were also region-specifically regulated. Thus, Spdef (SAM pointed domain-containing ETS transcription factor) was barely induced in distal airways but extensively in proximal airways in the acute (10-fold) and chronic model (4-fold). Along with this, Spdef-regulated FoxA3 showed higher induction in proximal compared to distal airways in the acute (7.6 vs. 4.3-fold) and the chronic (3.9 vs. 2.5-fold) asthma model.

These results suggest, that the lower expression of IL-13Rα1 and hence, the reduced sensitivity towards IL-13, might protect distal airways from mucus plugging and impaired ventilation of the attached alveoli.