Fluticasone propionate downregulates nasal fibroblast functions involved in airway inflammation and remodeling.
BACKGROUND
Besides being highly effective in the treatment of allergic and nonallergic rhinitis with eosinophilia, intranasal corticosteroids appear to be useful in reducing nasal polypoid lesions and the likelihood of polyp recurrence after surgery. We evaluated the ability of fluticasone propionate to downregulate fibroblast functions related to nasal inflammation and remodeling.


METHODS
Primary nasal polyp tissue-derived fibroblasts were stimulated with tumor necrosis factor (TNF)-alpha or interleukin (IL)-4 or basic fibroblast growth factor (bFGF) in the presence of fluticasone propionate (0.1-100 nM). Fibroblast proliferation, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression and eotaxin release were then evaluated.


RESULTS
As compared with unstimulated cultures, a significant increase in fibroblast proliferation was observed when the cells were stimulated with bFGF (p < 0.05), but not with TNF-alpha or IL-4 (p > 0.05). TNF-alpha induced an upregulation of ICAM-1 expression (p < 0.05), which was not seen in fibroblasts cultured in the presence of IL-4 or bFGF. No changes in VCAM-1 expression were induced by TNF-alpha, IL-4 or bFGF, whereas both TNF-alpha and IL-4 increased eotaxin release (p < 0.05). Both bFGF-induced fibroblast proliferation and TNF-alpha-induced ICAM-1 expression were significantly reduced by fluticasone, starting at the dose of 1 and 10 nM, respectively (p < 0.05). Fluticasone at concentrations of 1-100 nM effectively inhibited eotaxin release by TNF-alpha- or IL-4-stimulated fibroblasts (p < 0.05).


CONCLUSIONS
The pharmacologic activity of fluticasone in patients with chronic upper airway inflammatory disease may include inhibition of resident fibroblast functions involved in airway inflammation and remodeling.
Silvestri
M
M
Pulmonary Department, Giannina Gaslini Institute, Genoa, Italy.
Sabatini
F
F
Scarso
L
L
Cordone
A
A
Dasic
G
G
Rossi
G A
GA
D000287:Administration, Topical; D000328:Adult; D000730:Androstadienes / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000032:analysis / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000276:immunology / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D000068298:Fluticasone; D005938:Glucocorticoids; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000096:biosynthesis; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology; D008297:Male; D009298:Nasal Polyps / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000096:biosynthesis
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D016222:Fibroblast Growth Factor 2; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D000068298:Fluticasone