TY - JOUR
T1 - Role of metallothionein in lung inflammation induced by ozone exposure in mice
AU - Inoue, Ken ichiro
AU - Takano, Hirohisa
AU - Kaewamatawong, Theerayuth
AU - Shimada, Akinori
AU - Suzuki, Junko
AU - Yanagisawa, Rie
AU - Tasaka, Sadatomo
AU - Ishizaka, Akitoshi
AU - Satoh, Masahiko
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2008/12/15
Y1 - 2008/12/15
N2 - Metallothionein (MT) is a free radical scavenger induced by inflammatory stimuli; however, its roles in inflammation have not been fully investigated. In the present study, we genetically determined the role of MT in ozone (O3)-induced lung inflammation using MT-I/II null (-/-) mice. Subacute (65 h) exposure to O3 (0.3 ppm) induced lung inflammation and enhanced vascular permeability, which was significantly greater in MT(-/-) than in corresponding wild-type mice. Electron microscopically, O3 exposure induced vacuolar degeneration of pulmonary endothelial and epithelial cells, and interstitial edema with focal loss of the basement membrane, which was more prominent in MT(-/-) than in wild-type mice. O3 -induced lung expression of interleukin-6 was significantly greater in MT(-/-) than in wild-type mice; however, lung expression of the chemokines examined was comparable in both genotypes of mice in the presence of O3. Following O3 exposure, the formation of oxidative stress-related molecules/adducts, such as heme oxidase-1, inducible nitric oxide synthase, 8-hydroxy-2′-deoxyguanosine, and nitrotyrosine, in the lung was significantly greater in MT(-/-) than in wild-type mice. Collectively, MT protects against O3-induced lung inflammation, at least partly, via the regulation of pulmonary endothelial and epithelial integrity and its antioxidative property.
AB - Metallothionein (MT) is a free radical scavenger induced by inflammatory stimuli; however, its roles in inflammation have not been fully investigated. In the present study, we genetically determined the role of MT in ozone (O3)-induced lung inflammation using MT-I/II null (-/-) mice. Subacute (65 h) exposure to O3 (0.3 ppm) induced lung inflammation and enhanced vascular permeability, which was significantly greater in MT(-/-) than in corresponding wild-type mice. Electron microscopically, O3 exposure induced vacuolar degeneration of pulmonary endothelial and epithelial cells, and interstitial edema with focal loss of the basement membrane, which was more prominent in MT(-/-) than in wild-type mice. O3 -induced lung expression of interleukin-6 was significantly greater in MT(-/-) than in wild-type mice; however, lung expression of the chemokines examined was comparable in both genotypes of mice in the presence of O3. Following O3 exposure, the formation of oxidative stress-related molecules/adducts, such as heme oxidase-1, inducible nitric oxide synthase, 8-hydroxy-2′-deoxyguanosine, and nitrotyrosine, in the lung was significantly greater in MT(-/-) than in wild-type mice. Collectively, MT protects against O3-induced lung inflammation, at least partly, via the regulation of pulmonary endothelial and epithelial integrity and its antioxidative property.
KW - Lung inflammation
KW - Metallothionein
KW - Oxidative stress
KW - Ozone
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U2 - 10.1016/j.freeradbiomed.2008.09.008
DO - 10.1016/j.freeradbiomed.2008.09.008
M3 - Article
C2 - 18929643
AN - SCOPUS:56349115845
SN - 0891-5849
VL - 45
SP - 1714
EP - 1722
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 12
ER -