International Immunology Advance Access published online on October 6, 2005
International Immunology, doi:10.1093/intimm/dxh325
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1 Institut National de la Santé et de la Recherche Médicale 506, Bat. Lavoisier, Hospital Paul Brousse, Villejuif, France
* To whom correspondence should be addressed. 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
Received November 10, 2004
Accepted August 23, 2005
Article
Lung myofibroblasts as targets of salmeterol and fluticasone propionate: inhibition of
-SMA and NF-
B
2 Institut National de la Santé et de la Recherche Médicale 506, Bat. Lavoisier, Hospital Paul Brousse, Villejuif, France; Institut National de la Santé et de la Recherche Médicale Unité 542, Bat. Lavoisier, Hospital Paul Brousse, Villejuif, France
3 Institut National de la Santé et de la Recherche Médicale Unité 542, Bat. Lavoisier, Hospital Paul Brousse, Villejuif, France
4 Department of Allergy and Respiratory Diseases, Department of Internal Medicine, University of Genoa, Genoa, Italy
5 Medical Department, Glaxo SmithKline, Verona, Italy
6 Department of Pathology, Faculty of Medicine, 1211 Geneva 4, Switzerland
Bruno Azzarone, E-mail: bazzarone{at}hotmail.com
Abstract 
2-agonists associated or not to inhaled corticosteroids, investigating their effects on (i) the constitutive and transforming growth factor- (TGF-)-induced expression of 
-smooth muscle actin (-SMA), the main functional marker of myofibroblastic differentiation and contractility; (ii) isometric contraction and (iii) tumour necrosis factor- (TNF-)-induced nuclear translocation of the pro-inflammatory transcription factor nuclear factor-
B (NF-B). The 2-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--induced expression of -SMA. Second, the two drugs block the TNF--induced nuclear translocation of the pro-inflammatory transcription factor NF-B. Finally, SMl decreases TNF- -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 2-agonists.2-agonists; airway inflammation; airway remodelling; asthma.
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