title: Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling.
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.
authors.affiliation: Pulmonary Division, G. Gaslini Institute, Largo G. Gaslini 5, 16147, Genoa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Sabatini
authors.forename: M
authors.initials: M
authors.lastname: Silvestri
authors.forename: R
authors.initials: R
authors.lastname: Sale
authors.forename: L
authors.initials: L
authors.lastname: Serpero
authors.forename: M
authors.initials: M
authors.lastname: Giuliani
authors.forename: L
authors.initials: L
authors.lastname: Scarso
authors.forename: P
authors.initials: P
authors.lastname: Favini
authors.forename: G A
authors.initials: GA
authors.lastname: Rossi
mesh_terms: D000402:Airway Obstruction / Q000503:physiopathology*; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D054413:Chemokine CCL11; D018932:Chemokine CCL2 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000166:cytology; D000068656:Mometasone Furoate; D011244:Pregnadienediols / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism
chemical_list: C515456:CCL11 protein, human; D015815:Cell Adhesion Molecules; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D019742:Chemokines, CC; D018960:Hyaluronan Receptors; D015850:Interleukin-6; D011244:Pregnadienediols; D016212:Transforming Growth Factor beta; D000068656:Mometasone Furoate; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone; D004247:DNA