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Opposite effect of corticosteroids and long‐acting β 2 ‐agonists on serum‐ and TGF‐β 1 ‐induced extracellular matrix deposition by primary human lung fibroblasts
Author(s) -
Goulet Stephanie,
Bihl Michel P.,
Gambazzi Franco,
Tamm Michael,
Roth Michael
Publication year - 2007
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20836
Subject(s) - extracellular matrix , fibroblast , ctgf , downregulation and upregulation , glucocorticoid receptor , endocrinology , medicine , chemistry , transforming growth factor , inflammation , glucocorticoid , receptor , growth factor , biochemistry , in vitro , gene
Asthma and chronic obstructive pulmonary disease (COPD) are characterized by chronic airway inflammation and major structural lung tissue changes including increased extracellular matrix (ECM) deposition. Inhaled corticosteroids and long‐acting β 2 ‐agonists (LABA) are the basic treatment for both diseases, but their effect on airway remodeling remains unclear. In this study, we investigated the effect of corticosteroids and LABA, alone or in combination, on total ECM and collagen deposition, gene expression, cell proliferation, and IL‐6, IL‐8, and TGF‐β 1 levels by primary human lung fibroblasts. In our model, fibroblasts in 0.3% albumin represented a non‐inflammatory condition and stimulation with 5% FCS and/or TGF‐β 1 mimicked an inflammatory environment with activation of tissue repair. FCS (5%) increased total ECM, collagen deposition, cell proliferation, and IL‐6, IL‐8, and TGF‐β 1 levels. In 0.3% albumin, corticosteroids reduced total ECM and collagen deposition, involving the glucocorticoid receptor (GR) and downregulation of collagen, heat shock protein 47 (Hsp47), and Fli1 mRNA expression. In 5% FCS, corticosteroids increased ECM deposition, involving upregulation of COL4A1 and CTGF mRNA expression. LABA reduced total ECM and collagen deposition under all conditions partly via the β 2 ‐adrenergic receptor. In combination, the drugs had an additive effect in the presence or absence of TGF‐β 1 further decreasing ECM deposition in 0.3% albumin whereas counteracting each other in 5% FCS. These data suggest that the effect of corticosteroids, but not of LABA, on ECM deposition by fibroblasts is altered by serum. These findings imply that as soon as airway inflammation is resolved, long‐term treatment with combined drugs may beneficially reduce pathological tissue remodeling. J. Cell. Physiol. 210: 167–176, 2007. © 2006 Wiley‐Liss, Inc.