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  • 1
    Electronic Resource
    Electronic Resource
    In vitro effects of flunisolide on MMP-9, TIMP-1, fibronectin, TGF-β1 release and apoptosis in sputum cells freshly isolated from mild to moderate asthmatics (2004)
    Oxford, UK : Munksgaard International Publishers
    Allergy 59 (2004), S. 0 
    Details
    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
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of low doses of inhaled fluticasone propionate on inflammation and remodelling in persistent-mild asthma (2005)
    Oxford, UK : Munksgaard International Publishers
    Allergy 60 (2005), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In asthma a dysregulation of eosinophil apoptosis and an imbalance of metalloproteinase-9 (MMP-9) and tissue inhibitor metalloproteinase-1 (TIMP-1) play an important role in airway inflammation and remodelling. We evaluated the effects of a low dose of inhaled fluticasone proprionate (FP) (100 μg bid by Diskus) for 4 weeks in 24 steroid naive patients with mild persistent asthma, symptomatic and with a sputum eosinophilia ≥3% on clinical outcomes and inflammatory markers such as the induced sputum eosinophils, the induced sputum apoptotic eosinophils, the levels of MMP-9 and TIMP-1 and their molar ratio in the induced sputum supernatants. After FP treatment forced expiratory volume (FEV1) and FEV1/forced vital capacity values, PEF (L/min), sputum apoptotic eosinophils, and MMP-9/TIMP-1 molar ratio in sputum supernatants of asthmatic subjects were significantly increased in comparison with baseline, while sputum eosinophils significantly decreased. Change (Δ) in FEV1 after treatment with FP negatively correlated with the Δ in sputum eosinophils, while the Δ in MMP-9 values positively correlated with Δ in TIMP-1 values. This study shows that the clinical improvement achieved by the use of low doses of FP in asthmatics is related, at least in part, to the resolution of eosinophilic inflammation and the downregulation of remodelling markers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.2005.00827.x
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  • 3
    Electronic Resource
    Electronic Resource
    Biochemical interaction between effects of beclomethasone dipropionate and salbutamol or formoterol in sputum cells from mild to moderate asthmatics (2005)
    Oxford, UK : Munksgaard International Publishers
    Allergy 60 (2005), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Several in vitro studies demonstrate that corticosteroids and long-acting β2 agonists may have a complementary and synergistic mode of action on the inflammatory processes in asthma.Methods:  Sputum was induced in 20 mild to moderate asthmatic patients and the induced sputum cells (ISC) were cultured with beclomethasone dipropionate (BDP) 10−7 M, salbutamol 10−8 M and formoterol 10−8 M either alone or in combination, BDP plus salbutamol and BDP plus formoterol, for 24 h. We measured the levels of growth macrophages-colony stimulating factor (GM-CSF), released on activation normal T cells expressed and activated (RANTES) and interleukin-8 (IL-8), in the supernatant of stimulated cells by ELISA. Furthermore, we assessed nuclear translocation of glucocorticoid receptor (GR) and the expression of β2 receptor in ISC by immunofluorescence and RT-PCR, respectively.Results:  The release of GM-CSF, RANTES and IL-8 in ISC was significantly reduced by BDP plus salbutamol or formoterol as compared with either drug alone (P 〈 0.0001). β2 receptor expression was increased after 30 min of incubation with BDP and continued to increase over a time period of 4 h (P 〈 0.0001). Furthermore after 30 min of incubation, nuclear translocation of GR was greater with BDP plus salbutamol or formoterol than with any of the drugs alone (P 〈 0.0001).Conclusion:  The present ex vivo study demonstrates a complementary mode of action between BDP and salbutamol or formoterol leading to an enhanced anti-inflammatory activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.2005.00702.x
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    Paper (German National Licenses)
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