ISSN:
1398-9995
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Background: Corticosteroids play an important role in inflammation and remodelling of airways and are considered an important therapeutic target in asthma. Inflammation in asthma is characterized by a dysregulation of eosinophil apoptosis and of markers of airways remodelling. We evaluated the ability of flunisolide to inhibit in vitro the release of metalloproteinases-9 (MMP-9), tissue inhibitor metalloproteinases-1 (TIMP-1), transforming growth factor (TGF-β) and fibronectin by sputum cells (SC) as well as to induce sputum eosinophil apoptosis.Methods: The SC, isolated from induced sputum samples of 12 mild-to-moderate asthmatics, were cultured for 24 h in the presence or absence of flunisolide (1, 10 and 100 μM). The release of mediators was assessed by enzyme-linked immunosorbent assay (ELISA) whereas apoptosis was studied by TUNEL technique.Results: Flunisolide (10 μM) significantly reduced MMP-9 and TIMP-1 (P = 0.0011 and P 〈 0.0001 respectively) and increased MMP-9/TIMP-1 molar ratio (P = 0.004). In addition, flunisolide decreased TGF-β and fibronectin release by SC (P = 0.006; and P 〈 0.0001 respectively) and increased eosinophil apoptosis (P 〈 0.001).Conclusions: These results demonstrate that flunisolide may play an important role in the inhibition of airway inflammation and remodelling, by promoting the resolution of eosinophilic inflammation and by inhibiting the release of MMP-9, TIMP-1, TGF-β and fibronectin.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1398-9995.2004.00516.x
