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A murine model of toluene diisocyanate-induced asthma can be treated with matrix metalloproteinase inhibitor.

Lee, YC; Song, CH; Lee, HB; Oh, JL; Rhee, YK; Park, HS; Koh, GY
The Journal of allergy and clinical immunology, 108(6):1021-1026, 2001
Journal Title
The Journal of allergy and clinical immunology
BACKGROUND: Toluene diisocyanate (TDI) is a leading cause of occupational asthma. TDI-induced asthma is an inflammatory disease of the airways that is associated with airway remodeling. However, there are little data available on the role of matrix metalloproteinases (MMPs) in TDI-induced asthma.

OBJECTIVE: We evaluated whether MMP-9 participates in the airway inflammation in TDI-induced asthma. An additional aim of the present study was to determine whether MMP inhibitors could be effective therapeutic agents for TDI-induced asthma.

METHODS: We developed a murine model of TDI-induced asthma to examine the involvement of MMPs by performing 2 sensitizations with 3% TDI and 1 challenge with 1% TDI using ultrasonic nebulization.

RESULTS: Murine TDI-induced asthma includes findings of (1) increased inflammatory cells, including neutrophils, lymphocytes, and eosinophils; (2) histologic changes, including infiltration of inflammatory cells around bronchioles, thickened airway epithelium, and accumulation of mucus and debris in the bronchioles; (3) increased MMP-9 activity in inflammatory cells in the airway lumen; and (4) airway hyperresponsiveness. Administration of an MMP inhibitor remarkably reduced all these pathophysiologic findings.

CONCLUSION: We conclude that TDI-induced occupational asthma is associated with the induction of MMP-9 in inflammatory cells, and the inhibition of MMP-9 may be a good therapeutic strategy.
MeSH terms
AnimalsAsthma/chemically inducedAsthma/drug therapy*Bronchoalveolar Lavage Fluid/cytologyDisease Models, AnimalFemaleMatrix Metalloproteinase 9/antagonists & inhibitors*Matrix Metalloproteinase 9/physiologyMiceMice, Inbred BALB CProtease Inhibitors/therapeutic use*Toluene 2,4-Diisocyanate/toxicity*
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Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
AJOU Authors
박, 해심
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