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Matrix metalloproteinases-7, -8, -9 and TIMP-1 in the follow-up of diisocyanate-induced asthma
P Piirilä1, A Lauhio, M-L Majuri
1Laboratory of Clinical Physiology, Helsinki University Hospital, Helsinki, Finland.
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.
Insights
In diisocyanate-induced asthma (DIA) patients, inhaled steroids increased matrix metalloproteinase-9 (MMP-9) and decreased MMP-7. Elevated MMP-9 correlated with reduced TH-2 inflammation, suggesting a protective role.
Area of Science:
- Respiratory Medicine
- Immunology
- Biochemistry
Background:
- Diisocyanate-induced asthma (DIA) is linked to poor prognosis.
- Investigating matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases (TIMP-1) in DIA outcomes.
- Assessing the role of MMP-7, MMP-8, MMP-9, and TIMP-1 in DIA patients.
Purpose of the Study:
- To clarify the association of MMP-7, MMP-8, MMP-9, and TIMP-1 with functional and inflammatory outcomes in DIA patients.
- To evaluate the impact of inhaled steroid therapy on these biomarkers and inflammation.
- To compare DIA patients with healthy controls.
Main Methods:
- Longitudinal study of 17 DIA patients diagnosed via specific challenge tests.
- Assessed spirometry, histamine challenge, and bronchoscopy.
- Measured MMPs and TIMP-1 in bronchoalveolar lavage (BAL) fluid using ELISA and zymography; also measured inflammatory cytokines.
- Repeated examinations after 6 months and 3 years of inhaled steroid treatment.
Main Results:
- Inhaled steroids increased BAL levels of MMP-9 and MMP-9/TIMP-1.
- Inhaled steroids decreased BAL levels of MMP-7 and MMP-7/TIMP-1.
- Increased MMP-9 levels were associated with a decline in TH-2 type inflammation.
Conclusions:
- Reduced TH-2 inflammation in DIA post-steroid treatment correlates with elevated BAL MMP-9 and MMP-9/TIMP-1.
- Macrophage inhibitory factor (MIF) may induce MMP-9.
- MMP-9 might play a protective role in diisocyanate-induced asthma.
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