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% O(2). 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.