Opposite effect of fluticasone and salmeterol on fibronectin and tenascin-C expression in primary human lung fibroblasts

Authors


Correspondence:
Ruth Chiquet-Ehrismann, Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Maulbeerstrasse 66, CH-4058 Basel, Switzerland. E-mail: chiquet@fmi.ch

Summary

Background Airway remodelling is a key feature of asthma and chronic obstructive pulmonary disease (COPD). The remodelling process involves the deposition of extracellular matrix (ECM) proteins within the airways. Current therapies for asthma and COPD consist of inhaled corticosteroids and long-acting β2-agonists (LABA). However, their effect on airway remodelling is not well understood so far.

Objective In this study we investigated the effect of fluticasone and salmeterol, either alone or in combination, on fibronectin and tenascin-C protein, isoform, and mRNA levels in primary human lung fibroblasts.

Methods In our model, fibroblasts cultured in serum-free medium represented a non-inflammatory condition and stimulation with 5% fetal calf serum and/or TGF-β1 mimicked a pro-fibrotic environment with activation of tissue repair. Using these two different conditions, the effects of fluticasone and salmeterol on fibronectin and tenascin-C protein and mRNA levels were analysed by immunoblotting and semi-quantitative RT-PCR.

Results In both conditions, fluticasone increased fibronectin transcript and protein levels, whereas it decreased those of tenascin-C. Salmeterol neither affected fibronectin and tenascin-C synthesis significantly nor did it influence the effect of fluticasone when applied in combination. Furthermore, we found that treatment with fluticasone had an opposite effect on extra domain A and B containing fibronectin isoforms generated by alternative splicing compared with total fibronectin transcript levels, whereas tenascin-C isoforms were not differently modulated by fluticasone.

Conclusions Our results indicate that standard therapies for inflammatory lung disorders influence ECM protein composition and relative expression levels. In contrast to corticosteroids, LABA did not significantly alter the expression of tenascin-C and fibronectin in cultures of primary human lung fibroblasts.

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