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

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37 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1714-1722
Number of pages9
JournalFree Radical Biology and Medicine
Volume45
Issue number12
DOIs
Publication statusPublished - 2008 Dec 15

Keywords

  • Lung inflammation
  • Metallothionein
  • Oxidative stress
  • Ozone

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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  • Cite this

    Inoue, K. I., Takano, H., Kaewamatawong, T., Shimada, A., Suzuki, J., Yanagisawa, R., Tasaka, S., Ishizaka, A., & Satoh, M. (2008). Role of metallothionein in lung inflammation induced by ozone exposure in mice. Free Radical Biology and Medicine, 45(12), 1714-1722. https://doi.org/10.1016/j.freeradbiomed.2008.09.008