Role of metallothionein in lung inflammation induced by ozone exposure in mice

Ken ichiro Inoue, Hirohisa Takano, Theerayuth Kaewamatawong, Akinori Shimada, Junko Suzuki, Rie Yanagisawa, Sadatomo Tasaka, Akitoshi Ishizaka, Masahiko Satoh

研究成果: Article査読

37 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1714-1722
ページ数9
ジャーナルFree Radical Biology and Medicine
45
12
DOI
出版ステータスPublished - 2008 12 15

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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