Matrix metalloproteinases-7, -8, -9 and TIMP-1 in the follow-up of diisocyanate-induced asthma.

Abstract

BACKGROUND:

Diisocyanate-induced asthma (DIA) is known to be associated with poor prognosis. We wished to clarify if matrix metalloproteinases (MMP)-7, -8 or -9 or tissue inhibitor of matrix metalloproteinases (TIMP-1) are associated with the functional or inflammatory outcome in DIA patients.

METHODS:

This is a longitudinal study where 17 patients with DIA diagnosed by a specific challenge test to diisocyanates were monitored. Exposure to diisocyanates was terminated seven (mean) months before the challenge test. The studies included spirometry, histamine challenge test and bronchoscopy. MMP-7, MMP-8, TIMP-1 [Enzyme-linked immunosorbent assay (ELISA)- and immunofluorometric assay-methods], MMP-9 (ELISA and zymography), interferon-gamma, tumour necrosis factor-alpha, interleukin-6, -8, -15, -17, CXCL-5/ENA-78, monocyte chemoattractant protein-1 and macrophage inhibitory factor (MIF) (ELISA) were assayed from bronchoalveolar lavage (BAL) fluid. Inhaled steroid therapy was initiated after the examinations, which were repeated at 6 months and at 3 years during the treatment. The results were compared with those of 15 healthy controls.

RESULTS:

Inhaled steroid medication increased BAL levels of MMP-9 and MMP-9/TIMP-1 and decreased MMP-7 and MMP-7/TIMP-1. The increase in MMP-9 levels was associated with a decline in the TH-2 type inflammation.

CONCLUSIONS:

Our data suggest that reduced TH-2 type inflammation in DIA after inhaled steroid medication is reflected as elevated MMP-9 and MMP-9/TIMP-1 levels in BAL. MIF may be the inducer of MMP-9. This might point to some protective role for MMP-9 in DIA.

• Authors: P Piirilä, A Lauhio, M-L Majuri, A Meuronen, M Myllärniemi, T Tervahartiala, K Vuorinen, A Laitinen, H Alenius, V L Kinnula, T Sorsa
• Journal: Allergy (Allergy) Vol. 65 Issue 1 Pg. 61-8 (Jan 2010) ISSN: 1398-9995 [Electronic] Denmark
• PMID: 19804449 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenal Cortex Hormones
• Anti-Asthmatic Agents
• Biomarkers
• Cytokines
• Inflammation Mediators
• Tissue Inhibitor of Metalloproteinase-1
• Matrix Metalloproteinase 7
• Matrix Metalloproteinase 8
• Matrix Metalloproteinase 9

Topics

• Adrenal Cortex Hormones (therapeutic use)
• Adult
• Anti-Asthmatic Agents (therapeutic use)
• Asthma (diagnosis, drug therapy, etiology, metabolism)
• Biomarkers
• Bronchoalveolar Lavage Fluid
• Case-Control Studies
• Cytokines (metabolism)
• Female
• Follow-Up Studies
• Humans
• Inflammation Mediators (metabolism)
• Male
• Matrix Metalloproteinase 7
• Matrix Metalloproteinase 8
• Matrix Metalloproteinase 9
• Middle Aged
• Respiratory Function Tests
• Risk Factors
• Th2 Cells (immunology, metabolism)
• Tissue Inhibitor of Metalloproteinase-1