Matrix metalloproteinases-7, -8, -9 and TIMP-1 in the follow-up of diisocyanate-induced asthma |
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Authors: | P. Piirilä ,A. Lauhio,M.-L. Majuri,A. Meuronen,M. Myllä rniemi,T. Tervahartiala,K. Vuorinen,A. Laitinen,H. Alenius,V. L. Kinnula,& T. Sorsa |
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Affiliation: | Laboratory of Clinical Physiology, Helsinki University Hospital;;Department of Infectious Diseases, Helsinki University Hospital;;Unit of Excellence in Immunotoxicology, Finnish Institute of Occupational Health;;Department of Anatomy, University of Helsinki;;Department of Pulmonary Medicine, Helsinki University Hospital;;Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital;;Institute of Dentistry, University of Helsinki, Helsinki, Finland |
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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. |
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Keywords: | Diisocyanate-induced asthma inflammation inhaled steroids matrix metalloproteinase-9 |
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