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


CONCLUSIONS
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.
Lee
Y C
YC
Department of Internal Medicine, Chonbuk National University Medical School, Chonju, South Korea.
Song
C H
CH
Lee
H B
HB
Oh
J L
JL
Rhee
Y K
YK
Park
H S
HS
Koh
G Y
GY
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D005260:Female; D020780:Matrix Metalloproteinase 9 / Q000502:physiology; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D011480:Protease Inhibitors / Q000627:therapeutic use*; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity*
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D014051:Toluene 2,4-Diisocyanate; D020780:Matrix Metalloproteinase 9