Metalloproteinase-9 is increased after toluene diisocyanate exposure in the induced sputum from patients with toluene diisocyanate-induced asthma

• Published in: Clinical and experimental allergy Vol. 33; no. 1; pp. 113 - 118
• Main Authors: Park, H.-S., Kim, H.-A., Jung, J.-W., Kim, Y.-K., Lee, S.-K., Kim, S.-S., Nahm, D.-H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.01.2003; Blackwell; Wiley Subscription Services, Inc
• Subjects: Adult; Allergic diseases; Asthma - chemically induced; Asthma - enzymology; Biological and medical sciences; Bronchial Provocation Tests; Bronchoconstrictor Agents; Case-Control Studies; Female; Gelatinases - analysis; Humans; Immunopathology; Irritants - adverse effects; Lung - physiopathology; Male; Matrix Metalloproteinase 2 - analysis; Matrix Metalloproteinase 9 - analysis; Matrix Metalloproteinase 9 - blood; Medical sciences; Methacholine Chloride; Middle Aged; MMP-9; Occupational Diseases - chemically induced; Occupational Diseases - enzymology; Respiratory and ent allergic diseases; sputum; Sputum - chemistry; TDI-induced asthma; TIMP-1; Tissue Inhibitor of Metalloproteinase-1 - analysis; Tissue Inhibitor of Metalloproteinase-1 - blood; Toluene 2,4-Diisocyanate - adverse effects; Human; Immunopathology; Allergy; TIMP-1; Respiratory disease; Pathogenesis; Enzyme inhibitor; TDI-induced asthma; Inflammation; sputum; Remodeling; Asthma; Respiratory tract; Gelatin; Toluene derivatives; Obstructive pulmonary disease; Molecular biology; ELISA assay; MMP-9; Allergen
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1046/j.1365-2222.2003.01563.x

Summary Background and objective Persistent asthma symptoms are associated with airway inflammation and remodeling, which may be mediated through metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP). The aim of this study was to evaluate MMPs and TIMP involvement in toluene diisocyanate (TDI)‐induced asthma. Materials and method Induced sputum was collected in eight newly diagnosed TDI‐induced asthma subjects (group I) before and 7 h after the TDI and placebo challenges and in 12 subjects with TDI‐induced occupational asthma diagnosed 5 years previously with persistent asthma symptoms (group II). Sera was collected in group I at diagnosis, and in group II, they were collected at the time of the study. 12 nonasthmatic healthy subjects were enrolled as controls. MMP‐9, MMP‐2 and TIMP‐1 levels in both sputum and serum were measured by enzyme‐linked immunosorbent assay (ELISA). Gelatinase activity in the sputum was confirmed by zymographic analysis. Results The serum TIMP‐1 level was significantly higher in asthma patients than in healthy controls (P = 0.01), while MMP‐9 level was significantly lower in asthmatic patients (P = 0.03). There was no significant difference in MMP‐2 level (P = 0.27). MMP‐9 level in the sputum was significantly increased after the TDI challenges (P = 0.01). TIMP‐1 level in sputum tended to increase after TDI challenges, but no statistical significance was noted (P = 0.09). MMP‐9 and MMP‐9/TIMP‐1 levels in the sputum were significantly higher in group II than in group I (P = 0.04, P = 0.02) with no significant difference in TIMP‐1 level. Minimal amount of MMP‐2 was found in sputum. Zymography demonstrated that MMP‐9 level increased and active form of MMP‐9 was generated after the TDI bronchoprovocation test. Conclusion TDI exposure leads to overproduction of MMP‐9, which may induce airway inflammation and remodeling, and then contribute to persistent asthmatic symptoms in TDI‐induced asthma.