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Inhaled corticosteroids decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in asthma.
J Allergy Clin Immunol. 1999 Aug; 104(2 Pt 1):356-63.JA

Abstract

BACKGROUND

Bronchial asthma is characterized by airway wall remodeling. Matrix metalloproteinases (MMPs) are members of a family of proteolytic enzymes that degrade the extracellular matrix and that restrain the effects of their tissue inhibitors (TIMPs). Treatment with inhaled corticosteroids may prevent airway remodeling in asthma. However, the effects of corticosteroid treatment on MMPs and TIMPs in asthma are unknown.

OBJECTIVE

We examined the effects of inhaled beclomethasone dipropionate (BDP) on the expression of MMP-9 and TIMP-1 and subepithelial collagen deposition in bronchial biopsy specimens from 30 subjects with asthma.

METHODS

Inhaled BDP, 800 microg daily, or placebo was administered for 6 months in a double-blind, parallel-group study, and bronchial biopsies were performed before and after treatment. Biopsy specimens were examined for extent of collagen type III in the subepithelial basement membrane by means of immunohistochemistry, and expression of both epithelial and submucosal MMP-9 and TIMP-1 was quantitated. Numbers of inflammatory cells were also determined.

RESULTS

We observed significant decreases in collagen type III deposition (P <.01) and the expression of submucosal MMP-9 (P <.01) and a significant increase in the expression of submucosal TIMP-1 (P <.05) in the BDP group. Significant correlations were found between the subepithelial collagen type III deposition and epithelial (r (s) = 0.37, P <.05) and submucosal expression of MMP-9 (r (s) = 0.47, P <.01). Additionally, the number of many inflammatory cells and myofibroblasts in airway mucosa were significantly decreased in the BDP group.

CONCLUSION

Our findings suggest that corticosteroid treatment of asthma can reduce subepithelial collagen deposition by downregulation of MMP-9 expression and upregulation of TIMP-1 expression.

Authors+Show Affiliations

Second Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

10452757

Citation

Hoshino, M, et al. "Inhaled Corticosteroids Decrease Subepithelial Collagen Deposition By Modulation of the Balance Between Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 Expression in Asthma." The Journal of Allergy and Clinical Immunology, vol. 104, no. 2 Pt 1, 1999, pp. 356-63.
Hoshino M, Takahashi M, Takai Y, et al. Inhaled corticosteroids decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in asthma. J Allergy Clin Immunol. 1999;104(2 Pt 1):356-63.
Hoshino, M., Takahashi, M., Takai, Y., & Sim, J. (1999). Inhaled corticosteroids decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in asthma. The Journal of Allergy and Clinical Immunology, 104(2 Pt 1), 356-63.
Hoshino M, et al. Inhaled Corticosteroids Decrease Subepithelial Collagen Deposition By Modulation of the Balance Between Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 Expression in Asthma. J Allergy Clin Immunol. 1999;104(2 Pt 1):356-63. PubMed PMID: 10452757.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhaled corticosteroids decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in asthma. AU - Hoshino,M, AU - Takahashi,M, AU - Takai,Y, AU - Sim,J, PY - 1999/8/19/pubmed PY - 2000/2/19/medline PY - 1999/8/19/entrez SP - 356 EP - 63 JF - The Journal of allergy and clinical immunology JO - J Allergy Clin Immunol VL - 104 IS - 2 Pt 1 N2 - BACKGROUND: Bronchial asthma is characterized by airway wall remodeling. Matrix metalloproteinases (MMPs) are members of a family of proteolytic enzymes that degrade the extracellular matrix and that restrain the effects of their tissue inhibitors (TIMPs). Treatment with inhaled corticosteroids may prevent airway remodeling in asthma. However, the effects of corticosteroid treatment on MMPs and TIMPs in asthma are unknown. OBJECTIVE: We examined the effects of inhaled beclomethasone dipropionate (BDP) on the expression of MMP-9 and TIMP-1 and subepithelial collagen deposition in bronchial biopsy specimens from 30 subjects with asthma. METHODS: Inhaled BDP, 800 microg daily, or placebo was administered for 6 months in a double-blind, parallel-group study, and bronchial biopsies were performed before and after treatment. Biopsy specimens were examined for extent of collagen type III in the subepithelial basement membrane by means of immunohistochemistry, and expression of both epithelial and submucosal MMP-9 and TIMP-1 was quantitated. Numbers of inflammatory cells were also determined. RESULTS: We observed significant decreases in collagen type III deposition (P <.01) and the expression of submucosal MMP-9 (P <.01) and a significant increase in the expression of submucosal TIMP-1 (P <.05) in the BDP group. Significant correlations were found between the subepithelial collagen type III deposition and epithelial (r (s) = 0.37, P <.05) and submucosal expression of MMP-9 (r (s) = 0.47, P <.01). Additionally, the number of many inflammatory cells and myofibroblasts in airway mucosa were significantly decreased in the BDP group. CONCLUSION: Our findings suggest that corticosteroid treatment of asthma can reduce subepithelial collagen deposition by downregulation of MMP-9 expression and upregulation of TIMP-1 expression. SN - 0091-6749 UR - https://www.unboundmedicine.com/medline/citation/10452757/Inhaled_corticosteroids_decrease_subepithelial_collagen_deposition_by_modulation_of_the_balance_between_matrix_metalloproteinase_9_and_tissue_inhibitor_of_metalloproteinase_1_expression_in_asthma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(99)70379-9 DB - PRIME DP - Unbound Medicine ER -