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

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25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1119-1126
Number of pages8
JournalFree Radical Biology and Medicine
Volume46
Issue number8
DOIs
Publication statusPublished - 2009 Apr 15

Keywords

  • Bach1
  • Bronchoalveolar lavage
  • Chromatin immunoprecipitation analysis
  • Free radicals
  • Heme oxygenase-1
  • Hyperoxic lung injury
  • IL-6
  • Oxidative stress
  • Small interfering RNA
  • Survival

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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  • Cite this

    Tanimoto, T., Hattori, N., Senoo, T., Furonaka, M., Ishikawa, N., Fujitaka, K., Haruta, Y., Yokoyama, A., Igarashi, K., & Kohno, N. (2009). Genetic ablation of the Bach1 gene reduces hyperoxic lung injury in mice: Role of IL-6. Free Radical Biology and Medicine, 46(8), 1119-1126. https://doi.org/10.1016/j.freeradbiomed.2009.01.017