Publication

Differential effects of fluticasone on extracellular matrix production by airway and parenchymal fibroblasts in severe COPD

Brandsma, C-A., Timens, W., Jonker, M. R., Rutgers, B., Noordhoek, J. A. & Postma, D. S., Oct-2013, In : American Journal of Physiology - Lung Cellular and Molecular Physiology. 305, 8, p. L582-L589 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

Chronic obstructive pulmonary disease (COPD) is characterized by abnormal repair in the lung resulting in airway obstruction associated with emphysema and peripheral airway fibrosis. Because the presence and degree of airways disease and emphysema varies between COPD patients, this may explain the heterogeneity in the response to treatment. It is currently unknown whether and to what extent inhaled steroids can affect the abnormal repair process in the airways and lung parenchyma in COPD. We investigated the effects of fluticasone on transforming growth factor (TGF)-beta- and cigarette smoke-induced changes in mothers against decapentaplegic homolog (Smad) signaling and extracellular matrix (ECM) production in airway and parenchymal lung fibroblasts from patients with severe COPD. We showed that TGF-beta-induced ECM production by pulmonary fibroblasts, but not activation of the Smad pathway, was sensitive to the effects of fluticasone. Fluticasone induced decorin production by airway fibroblasts and partly reversed the negative effects of TGF-beta treatment. Fluticasone inhibited biglycan production in both airway and parenchymal fibroblasts and procollagen 1 production only in parenchymal fibroblasts, thereby restoring the basal difference in procollagen 1 production between airway and parenchymal fibroblasts. Our findings suggest that the effects of steroids on the airway compartment may be beneficial for patients with severe COPD, i.e., restoration of decorin loss around the airways, whereas the effects of steroids on the parenchyma may be detrimental, since the tissue repair response, i.e., biglycan and procollagen production, is inhibited. More research is needed to further disentangle these differential effects of steroid treatment on the different lung compartments and its impact on tissue repair and remodeling in COPD.

Original languageEnglish
Pages (from-to)L582-L589
Number of pages8
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume305
Issue number8
Publication statusPublished - Oct-2013

    Keywords

  • chronic obstructive pulmonary disease, tissue repair and remodeling, OBSTRUCTIVE PULMONARY-DISEASE, HUMAN LUNG FIBROBLASTS, GENE-EXPRESSION, TRIAL, SALMETEROL, DEPOSITION, EMPHYSEMA

ID: 5975166