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Effects of inhaled corticosteroids on metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 in the airways of asthmatic children.
Int Arch Allergy Immunol. 2010; 151(3):247-54.IA

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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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Authors+Show Affiliations

Obase Y
Department of Allergy, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland. obaseya@yahoo.co.jp
Rytilä P
No affiliation info available
Metso T
No affiliation info available
Pelkonen AS
No affiliation info available
Tervahartiala T
No affiliation info available
Turpeinen M
No affiliation info available
Mäkelä M
No affiliation info available
Saarialho-Kere U
No affiliation info available
Selroos O
No affiliation info available
Sorsa T
No affiliation info available
Haahtela T
No affiliation info available

MeSH

Administration, InhalationAdolescentAdrenal Cortex HormonesAnti-Asthmatic AgentsAsthmaBudesonideChildChild, PreschoolFemaleHumansImmunohistochemistryLungMacrophagesMaleMatrix Metalloproteinase 8Respiratory Function TestsSputumTissue Inhibitor of Metalloproteinase-1

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19786805

Citation

Obase, Y, et al. "Effects of Inhaled Corticosteroids On Metalloproteinase-8 and Tissue Inhibitor of Metalloproteinase-1 in the Airways of Asthmatic Children." International Archives of Allergy and Immunology, vol. 151, no. 3, 2010, pp. 247-54.
Obase Y, Rytilä P, Metso T, et al. Effects of inhaled corticosteroids on metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 in the airways of asthmatic children. Int Arch Allergy Immunol. 2010;151(3):247-54.
Obase, Y., Rytilä, P., Metso, T., Pelkonen, A. S., Tervahartiala, T., Turpeinen, M., Mäkelä, M., Saarialho-Kere, U., Selroos, O., Sorsa, T., & Haahtela, T. (2010). Effects of inhaled corticosteroids on metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 in the airways of asthmatic children. International Archives of Allergy and Immunology, 151(3), 247-54. https://doi.org/10.1159/000242362
Obase Y, et al. Effects of Inhaled Corticosteroids On Metalloproteinase-8 and Tissue Inhibitor of Metalloproteinase-1 in the Airways of Asthmatic Children. Int Arch Allergy Immunol. 2010;151(3):247-54. PubMed PMID: 19786805.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of inhaled corticosteroids on metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 in the airways of asthmatic children. AU - Obase,Y, AU - Rytilä,P, AU - Metso,T, AU - Pelkonen,A S, AU - Tervahartiala,T, AU - Turpeinen,M, AU - Mäkelä,M, AU - Saarialho-Kere,U, AU - Selroos,O, AU - Sorsa,T, AU - Haahtela,T, Y1 - 2009/09/29/ PY - 2008/12/20/received PY - 2009/05/29/accepted PY - 2009/9/30/entrez PY - 2009/9/30/pubmed PY - 2010/4/1/medline SP - 247 EP - 54 JF - International archives of allergy and immunology JO - Int Arch Allergy Immunol VL - 151 IS - 3 N2 - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SN - 1423-0097 UR - https://www.unboundmedicine.com/medline/citation/19786805/Effects_of_inhaled_corticosteroids_on_metalloproteinase_8_and_tissue_inhibitor_of_metalloproteinase_1_in_the_airways_of_asthmatic_children_ L2 - https://www.karger.com?DOI=10.1159/000242362 DB - PRIME DP - Unbound Medicine ER -