HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cazes, E. Articles by Canonica, G. W. Search for Related Content PubMed PubMed Citation Articles by Cazes, E. Articles by Canonica, G. W.

Novel Anti-inflammatory Effects of the Inhaled Corticosteroid Fluticasone Propionate During Lung Myofibroblastic Differentiation¹

Eric Cazes^2,*, Julien Giron-Michel^2,*, Soria Baouz^*, Christelle Doucet^*, Francesca Cagnoni, Susanna Oddera, Marie Körner, Gorana Dasic, Renato Testi, Bruno Azzarone^3,* and Giorgio Walter Canonica

^* Institut National de la Santé et de la Recherche Médicale Unité 506, Hospital Paul Brousse, Villejuif, France; Department of Allergy and Respiratory Diseases, Department of Internal Medicine, University of Genoa, Genoa, Italy; Oncogenesis, Differentiation, and Signal Transduction Laboratory, Institut de Recherche sur le Cancer-Centre Nationale de la Recherche Scientifique, Villejuif, France; and Glaxo Wellcome, Medical Department, Verona, Italy

Asthma is characterized by an irreversible subepithelial fibrosis with the appearance of myofibroblasts, which can be now considered important early participants in inflammatory responses as well as potential targets for anti-inflammatory drugs. In this study, we show that fluticasone propionate (FP), a powerful inhaled corticosteroid (ICS), displays novel anti-inflammatory effects on human lung fibroblasts during their myofibroblastic differentiation. Indeed, FP inhibits in lung myofibroblasts, at a very early stage of differentiation, the activation of Janus kinase/STAT pathways induced by IL-13 (tyrosine kinase 2, STAT1, STAT3, STAT6, mitogen-activated protein kinase). Contrarily, in mildly or fully differentiated myofibroblastic cultures, FP still displays a potential anti-inflammatory activity even if it only inhibits tyrosine kinase 2 phosphorylation. Moreover, FP inhibits constitutive and TGF--induced expression of -smooth muscle actin, the main marker of myofibroblastic differentiation, both in very early and in mild differentiated myofibroblasts. Finally, FP displays an additional powerful anti-inflammatory effect, decreasing nuclear translocation of NF-B independent of the degree of myofibroblastic differentiation. These data 1) suggest that myofibroblasts are priority targets for ICS, which is able to revert them to a normal phenotype even if they appear to be already engaged in their differentiation, and 2) may help to explain why asthma is improved by an early ICS treatment, whereas advanced asthma is more resistant to these drugs.

This article has been cited by other articles:

				G. W. Canonica Treating Asthma as an Inflammatory Disease Chest, July 1, 2006; 130(1_suppl): 21S - 28S. [Abstract] [Full Text] [PDF]

				M. A. Birrell, S. Wong, E. L. Hardaker, M. C. Catley, K. McCluskie, M. Collins, S. Haj-Yahia, and M. G. Belvisi I{kappa}B Kinase-2-Independent and -Dependent Inflammation in Airway Disease Models: Relevance of IKK-2 Inhibition to the Clinic Mol. Pharmacol., June 1, 2006; 69(6): 1791 - 1800. [Abstract] [Full Text] [PDF]

				S. Baouz, J. Giron-Michel, B. Azzarone, M. Giuliani, F. Cagnoni, S. Olsson, R. Testi, G. Gabbiani, and G. W. Canonica Lung myofibroblasts as targets of salmeterol and fluticasone propionate: inhibition of {alpha}-SMA and NF-{kappa}B Int. Immunol., November 1, 2005; 17(11): 1473 - 1481. [Abstract] [Full Text] [PDF]