Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling

Pulm Pharmacol Ther. 2003;16(5):287-97. doi: 10.1016/S1094-5539(03)00068-3.

Abstract

Lung fibroblasts play a key role in the pathogenesis of airway inflammation and remodeling through the release of mediators and the expression of surface molecules connected with cell-cell and cell-extracellular matrix interaction. The aim of the study was to evaluate the inhibitory effect of two corticosteroids, mometasone furoate (MOM) and dexamethasone (DEX), respectively, on a variety of fibroblast functions: DNA synthesis and proliferation, expression of adhesion molecules [intercellular adhesion molecule-1 (ICAM-1, CD54) and hyaluronic cellular adhesion molecule (HCAM, CD44)] and release of chemokines/cytokines [monocyte chemoattractant protein (MCP)-1, eotaxin, interleukin (IL)-6 and transforming growth factor (TGF)-beta]. Cells from a human foetal lung fibroblast cell line (GM 06114) were stimulated with basic fibroblast growth factor (bFGF) or tumour necrosis factor (TNF)-alpha in the presence of different concentrations (0.01-100.0nM) of MOM or DEX. A significant increase in fibroblast DNA synthesis and proliferation was observed when the cells were stimulated with bFGF (p<0.05), whereas TNF-alpha induced a significant upregulation in ICAM-1 expression and in MCP-1, eotaxin and IL-6 release (p<0.05, each comparison). No changes in HCAM expression and in TGF-beta release were observed (p>0.05, each comparison). The addition of MOM or DEX at the beginning of the cell cultures induced a significant downregulation in fibroblast DNA synthesis and proliferation, ICAM-1 and HCAM expression and chemokine/cytokine release (p<0.05, each comparison). At all the concentrations tested, MOM was more effective than DEX in inhibiting ICAM-1 expression and MCP-1 release (p<0.05, each comparison), whereas no potency advantage for MOM was detected in DNA synthesis, cell proliferation, HCAM expression and in eotaxin, IL-6 and TGF-beta release (p>0.05, each comparisons). These results extend the profile of the anti-inflammatory activity of mometasone furoate to lung fibroblast functions involved in airway inflammation and remodeling.

MeSH terms

  • Airway Obstruction / physiopathology*
  • Cell Adhesion Molecules / drug effects
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Line
  • Chemokine CCL11
  • Chemokine CCL2 / metabolism
  • Chemokines, CC / metabolism
  • DNA / biosynthesis
  • DNA / drug effects
  • DNA / metabolism
  • Dexamethasone / antagonists & inhibitors
  • Dexamethasone / pharmacology*
  • Dose-Response Relationship, Drug
  • Fibroblasts / drug effects*
  • Fibroblasts / physiology*
  • Humans
  • Hyaluronan Receptors / drug effects
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism
  • Intercellular Adhesion Molecule-1 / drug effects
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-6 / metabolism
  • Lung / cytology
  • Mometasone Furoate
  • Pregnadienediols / antagonists & inhibitors
  • Pregnadienediols / pharmacology*
  • Transforming Growth Factor beta / drug effects
  • Transforming Growth Factor beta / metabolism

Substances

  • CCL11 protein, human
  • Cell Adhesion Molecules
  • Chemokine CCL11
  • Chemokine CCL2
  • Chemokines, CC
  • Hyaluronan Receptors
  • Interleukin-6
  • Pregnadienediols
  • Transforming Growth Factor beta
  • Mometasone Furoate
  • Intercellular Adhesion Molecule-1
  • Dexamethasone
  • DNA