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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.

Authors+Show Affiliations

Department of Allergy, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland. obaseya@yahoo.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -