Novel Anti-inflammatory Effects of the Inhaled Corticosteroid Fluticasone Propionate During Lung Myofibroblastic Differentiation
| Autor: | Eric Cazes, Christelle Doucet, Susanna Oddera, Gorana Dasic, Julien Giron-Michel, Bruno Azzarone, Soria Baouz, Giorgio Walter Canonica, Marie Körner, Renato Testi, Francesca Cagnoni |
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| Rok vydání: | 2001 |
| Předmět: |
Adult
STAT3 Transcription Factor Cellular differentiation Immunology Anti-Inflammatory Agents TYK2 Kinase Administration Inhalation Humans Immunology and Allergy Medicine STAT3 Protein kinase A Lung Cells Cultured Interleukin 4 Interleukin-13 Microscopy Confocal biology Reverse Transcriptase Polymerase Chain Reaction business.industry NF-kappa B Proteins Cell Differentiation Fibroblasts Protein-Tyrosine Kinases Actins Androstadienes DNA-Binding Proteins Tyrosine kinase 2 Interleukin 13 Trans-Activators biology.protein Fluticasone Interleukin-4 Janus kinase business |
| Zdroj: | The Journal of Immunology. 167:5329-5337 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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-β-induced expression of α-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-κB 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. |
| Databáze: | OpenAIRE |
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