title: Genetic ablation of Bach1 gene enhances recovery from hyperoxic lung injury in newborn mice via transient upregulation of inflammatory genes.
abstract: BACKGROUND
  BTB and CNC homology 1 (Bach1) is a transcriptional repressor of heme oxygenase (HO)-1. The effects of Bach1 disruption on hyperoxic lung injury in newborn mice have not been determined. We aimed to investigate the role of Bach1 in the newborns exposed to hyperoxia.
  
  
  METHODS
  Bach1-/-and WT newborn mice were exposed to 21% or 95% oxygen for 4 d and were then allowed to recover in room air. Lung histology was assessed and lung Bach1, HO-1, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 mRNA levels were evaluated using RT-PCR. Lung inflammatory cytokine levels were determined using cytometric bead arrays.
  
  
  RESULTS
  After 10 d recovery from neonatal hyperoxia, Bach1-/-mice showed improved lung alveolarization compared with WT. HO-1, IL-6, and MCP-1 mRNA levels and IL-6 and MCP-1 protein levels were significantly increased in the Bach1-/-lungs exposed to neonatal hyperoxia. Although an increase in apoptosis was observed in the Bach1-/-and WT lungs after neonatal hyperoxia, there were no differences in apoptosis between these groups.
  
  
  CONCLUSIONS
  Bach1-/-newborn mice were well-recovered from hyperoxia-induced lung injury. This effect is likely achieved by the antioxidant/anti-inflammatory activity of HO-1 or by the transient overexpression of proinflammatory cytokines.
authors.affiliation: Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Nagano
authors.affiliation: Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Ogawa
authors.affiliation: Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Motojima
authors.affiliation: Department of Pediatrics, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Go
authors.affiliation: Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Tamura
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Igarashi
authors.affiliation: Department of Pediatrics, The Warren Alpert Medical School of Brown University, Providence, Rhode Island.
authors.forename: Phyllis A
authors.initials: PA
authors.lastname: Dennery
authors.affiliation: Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Namba
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D051547:Heme Oxygenase-1 / Q000235:genetics; D007249:Inflammation / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics; D055370:Lung Injury / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012313:RNA / Q000235:genetics; D015854:Up-Regulation
chemical_list: C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D015850:Interleukin-6; D012313:RNA; D051547:Heme Oxygenase-1