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


METHODS
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.


CONCLUSIONS
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.
Park
H-S
HS
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea. hspark@madang.ajou.ac.kr
Kim
H-A
HA
Jung
J-W
JW
Kim
Y-K
YK
Lee
S-K
SK
Kim
S-S
SS
Nahm
D-H
DH
D000328:Adult; D001249:Asthma / Q000139:chemically induced* / Q000201:enzymology; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D016022:Case-Control Studies; D005260:Female; D018093:Gelatinases / Q000032:analysis; D006801:Humans; D007509:Irritants / Q000009:adverse effects*; D008168:Lung / Q000503:physiopathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis* / Q000097:blood; D016210:Methacholine Chloride; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced* / Q000201:enzymology; D013183:Sputum / Q000737:chemistry*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000097:blood; D014051:Toluene 2,4-Diisocyanate / Q000009:adverse effects*
D016085:Bronchoconstrictor Agents; D007509:Irritants; D019715:Tissue Inhibitor of Metalloproteinase-1; D016210:Methacholine Chloride; D014051:Toluene 2,4-Diisocyanate; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9