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Effects of inhaled ...
Effects of inhaled corticosteroids on metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 in the airways of asthmatic children
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Obase, Y (författare)
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Rytila, P (författare)
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Metso, T (författare)
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Pelkonen, AS (författare)
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Tervahartiala, T (författare)
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Turpeinen, M (författare)
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Makela, M (författare)
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Saarialho-Kere, U (författare)
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Selroos, O (författare)
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- Sorsa, T (författare)
- Karolinska Institutet
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Haahtela, T (författare)
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(creator_code:org_t)
- 2009-09-29
- 2010
- Engelska.
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 151:3, s. 247-254
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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- <i>Background:</i> The effects of corticosteroids on the level and expression of matrix metalloproteinase-8 (MMP-8; collagenase-2) and tissue inhibitors of metalloproteinases (TIMPs) in airway tissue are poorly characterized in vivo. <i>Methods:</i> We compared MMP-8 and TIMP-1 levels in induced sputum and their expression in airway inflammatory cells of healthy children (n = 27) and of children with newly diagnosed asthma with mild (n = 20) or moderate symptoms (n = 19), before and after 6 months of treatment with inhaled budesonide. <i>Results:</i> At baseline, MMP-8 was higher in asthmatic children with moderate symptoms, TIMP-1 was lower and the MMP-8/TIMP-1 ratio was higher in both groups of asthmatic children compared with controls. Inhaled budesonide increased TIMP-1 levels in both groups of asthmatic children and normalized the MMP-8/TIMP-1 ratio, and this paralleled the improvement in forced expiratory volume in 1 s in children with mild symptoms. At baseline, asthmatic children had significantly more MMP-8-positive macrophages than control children, whereas the number of TIMP-1-positive macrophages was almost the same. Budesonide decreased the percentage of MMP-8-positive macrophages and increased that of TIMP-1-positive macrophages; these changes were significant in asthmatic children with mild symptoms. <i>Conclusions:</i> Inhaled budesonide normalized the MMP-8/TIMP-1 ratio in asthmatic children by upregulation of TIMP-1 production and downregulation of MMP-8 production by airway macrophages. This change may be a biochemical marker of an effect on airway inflammation and possibly of an ongoing remodeling process that should be further investigated using biopsy specimens.
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Obase, Y
-
Rytila, P
-
Metso, T
-
Pelkonen, AS
-
Tervahartiala, T
-
Turpeinen, M
-
visa fler...
-
Makela, M
-
Saarialho-Kere, ...
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Selroos, O
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Sorsa, T
-
Haahtela, T
-
visa färre...
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Karolinska Institutet