Genetic ablation of the Bach1 gene reduces hyperoxic lung injury in mice: Role of IL-6

Takuya Tanimoto, Noboru Hattori, Tadashi Senoo, Makoto Furonaka, Nobuhisa Ishikawa, Kazunori Fujitaka, Yoshinori Haruta, Akihito Yokoyama, Kazuhiko Igarashi, Nobuoki Kohno

研究成果: Article査読

26 被引用数 (Scopus)

抄録

Bach1 is a transcriptional repressor of the heme oxygenase (HO)-1 gene. Bach1-null (Bach1-/-) mice are reported to be protected from myocardial ischemia/reperfusion injury; however, the effect of Bach1 disruption on another oxidative stress model of hyperoxic lung injury has yet to be determined. To investigate the role of Bach1 in hyperoxic lung injury, Bach1-/- mice and wild-type (WT) mice were exposed to 90% O2. During hyperoxic exposure, the survival of Bach1-/- mice was significantly longer than that of WT mice. However, the administration of zinc protoporphyrin, an inhibitor of HO-1 activity, did not change the mortality in either of the mice, thus suggesting that this protective effect was not mediated by an HO-1 overexpression in Bach1-/- mice. The indices of lung injury in the lungs of Bach1-/- mice were lower than those of WT mice; unexpectedly, however, the levels of IL-6 in bronchoalveolar lavage (BAL) fluid from Bach1-/- mice were significantly higher than those of WT mice. Interestingly, the intrapulmonary administration of small interfering RNA against IL-6 was shown to reduce the IL-6 levels in BAL fluids and shorten the survival in Bach1-/- mice during hyperoxic exposure. In addition, a chromatin immunoprecipitation analysis revealed the binding of Bach1 to the IL-6 promoter and its detachment after oxidative stress. Considering the previous observation that the transgenic mice overexpressing IL-6 are protected from hyperoxic lung injury, these results therefore indicate that IL-6 mediates an increased survival in Bach1-/- mice during hyperoxic exposure.

本文言語English
ページ(範囲)1119-1126
ページ数8
ジャーナルFree Radical Biology and Medicine
46
8
DOI
出版ステータスPublished - 2009 4 15

ASJC Scopus subject areas

  • 生化学
  • 生理学(医学)

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