Anti-proliferative and anti-remodelling effect of beclomethasone dipropionate, formoterol and salbutamol alone or in combination in primary human bronchial fibroblasts.
BACKGROUND
Bronchial asthma is characterized by lower airway inflammation and remodelling. Anti-inflammatory treatment with inhaled corticosteroids (ICS) provides the mainstay of asthma therapy together with bronchodilation induced by short- and long-acting inhaled beta(2)-agonists. Lower airway fibroblasts may play a critical role in airway inflammation and remodelling, suggesting that they might represent an important target for the major anti-asthmatic drugs. The aim of our study was to investigate the effects of beclomethasone dipropionate (BDP), salbutamol and formoterol either alone or in combination on in vitro cultures of human bronchial fibroblasts.


METHODS
Fibroblasts were cultured in the presence of pro-inflammatory and proliferative stimuli, BDP, salbutamol and formoterol. The effects of drugs on cell proliferation were ascertained by (3)H-thymidine incorporation. CD90 and CD44 expression were detected by flow cytometry and fibronectin secretion using the enzyme-linked immunosorbent assay technique.


RESULTS
This study showed that BDP alone has significant anti-proliferative effects on lung fibroblasts treated with basic fibroblast growth factor and the combination of BDP with formoterol or salbutamol strengthen these effects. Short-acting beta(2)-agonist (SABA) or long-acting beta(2)-agonist (LABA) by themselves did not show any significant effect on the different cultures. CD44 and CD90 expression and fibronectin production were modulated by pro-inflammatory and proliferative stimuli; the addition of the drugs brought them back near to the basal level.


CONCLUSIONS
From this in vitro study, we can conclude that BDP, when combined with salbutamol or formoterol, exhibits enhanced anti-remodelling activity in bronchial fibroblasts, providing new insights on the additive effects of ICS and SABAs and LABAs for asthma therapy.
Descalzi
D
D
Allergy and Respiratory Diseases, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Folli
C
C
Nicolini
G
G
Riccio
A M
AM
Gamalero
C
C
Scordamaglia
F
F
Canonica
G W
GW
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology*; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001507:Beclomethasone / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay; D004983:Ethanolamines / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D000068759:Formoterol Fumarate; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D018800:Thy-1 Antigens / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D004983:Ethanolamines; D005353:Fibronectins; D018960:Hyaluronan Receptors; D018800:Thy-1 Antigens; D001507:Beclomethasone; D000420:Albuterol; D000068759:Formoterol Fumarate