Lung myofibroblasts as targets of salmeterol and fluticasone propionate: inhibition of α-SMA and NF-κB

Soria Baouz, Julien Giron-Michel, Bruno Azzarone, Massimo Giuliani, Francesca Cagnoni, Susanna Olsson, Renato Testi, Giulio Gabbiani, G. Walter Canonica

Research output: Contribution to journalArticlepeer-review

Abstract

Lung myofibroblasts play a major role in the pathophysiology of asthma, contributing not only to tissue remodelling but also to airway inflammation. Nevertheless, only recently, attention has been focused on these cells as potential targets for anti-allergic drugs. Herein, we analysed the pharmacological response of lung myofibroblasts to β2-agonists associated or not to inhaled corticosteroids, investigating their effects on (i) the constitutive and transforming growth factor-β (TGF-β)-induced expression of α-smooth muscle actin (α-SMA), the main functional marker of myofibroblastic differentiation and contractility; (ii) isometric contraction and (iii) tumour necrosis factor-α (TNF-α)-induced nuclear translocation of the pro-inflammatory transcription factor nuclear factor-κB (NF-κB). The β2-agonist salmeterol (SMl) has on human lung myofibroblasts new direct anti-contractile/anti-inflammatory effects that are amplified by the combined use of low concentrations of the glucocorticoid fluticasone propionate (FP). First, SMl and/or FP (10-12 M) inhibits the constitutive and TGF-β-induced expression of α-SMA. Second, the two drugs block the TNF-α-induced nuclear translocation of the pro-inflammatory transcription factor NF-κB. Finally, SMl decreases TNF-α-induced production of the inflammatory cytokine IL-6. The complementary anti-inflammatory/ anti-contractile effects displayed by SMl and FP on lung myofibroblasts in vitro may be related to the improvement in lung function and symptom control obtained in vivo by the early use of low doses of glucocorticoids in combination with long-acting β2-agonists.

Original languageEnglish
Pages (from-to)1473-1481
Number of pages9
JournalInternational Immunology
Volume17
Issue number11
DOIs
Publication statusPublished - Nov 2005

Keywords

  • β-agonists
  • Airway inflammation
  • Airway remodelling
  • Asthma

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Lung myofibroblasts as targets of salmeterol and fluticasone propionate: inhibition of α-SMA and NF-κB'. Together they form a unique fingerprint.

Cite this