Publication Details

Disruption of Nrf2 impairs the resolution of hyperoxia-induced acute lung injury and inflammation in mice.

Authors:Reddy NM, Kleeberger SR, Kensler TW, Yamamoto M, Hassoun PM, Reddy SP
Title:Disruption of Nrf2 impairs the resolution of hyperoxia-induced acute lung injury and inflammation in mice.
Journal:Journal of immunology (Baltimore, Md. : 1950) Jun 2009 , Vol 182 , pp. 7264-71
Abstract:Aberrant tissue repair and persistent inflammation following oxidant-mediated acute lung injury (ALI) can lead to the development and progression of various pulmonary diseases, but the mechanisms underlying these processes remain unclear. Hyperoxia is widely used in the treatment of pulmonary diseases, but the effects of this oxidant exposure in patients undergoing recovery from ALI are not clearly understood. Nrf2 has emerged as a crucial transcription factor that regulates oxidant stress through the induction of several detoxifying enzymes and other proteins. Using an experimental model of hyperoxia-induced ALI, we have examined the role of oxidant stress in resolving lung injury and inflammation. We found that when exposed to sublethal (72 h) hyperoxia, Nrf2-deficient, but not wild-type mice, succumbed to death during recovery. When both genotypes were exposed to a shorter period of hyperoxia-induced ALI (48 h), the lungs of Nrf2-deficient mice during recovery exhibited persistent cellular injury, impaired alveolar and endothelial cell regeneration, and persistent cellular infiltration by macrophages and lymphocytes. Glutathione (GSH) supplementation in Nrf2-deficient mice immediately after hyperoxia remarkably restored their ability to recover from hyperoxia-induced damage in a manner similar to that of wild-type mice. Thus, the results of the present study indicate that the Nrf2-regulated transcriptional response and, particularly GSH synthesis, is critical for lung tissue repair and the resolution of inflammation in vivo and suggests that a dysfunctional Nrf2-GSH pathway may compromise these processes in vivo.   PUBMED: 19454723
Ontological Annotations:
  • D011506: Proteins (Publication, NCBO Annotator)
  • D002828: Choristoma (Publication, NCBO Annotator)
  • D005978: Glutathione (Publication, NCBO Annotator)
  • D005838: Genotype (Publication, NCBO Annotator)
  • D012038: Regeneration (Publication, NCBO Annotator)
  • D051379: Mice (Publication, NCBO Annotator)
  • D013812: Therapeutics (Publication, NCBO Annotator)
  • D014157: Transcription Factors (Publication, NCBO Annotator)
  • MP:0001845: abnormal inflammatory response (Publication, NCBO Annotator)
  • D042783: Endothelial Cells (Publication, NCBO Annotator)
  • D008168: Lung (Publication, NCBO Annotator)
  • D008962: Models, Theoretical (Publication, NCBO Annotator)
  • D001076: Aptitude (Publication, NCBO Annotator)
  • D010361: Patients (Publication, NCBO Annotator)
  • D003643: Death (Publication, NCBO Annotator)
  • D014947: Wounds and Injuries (Publication, NCBO Annotator)
  • GO:0009058: biosynthetic process (Publication, NCBO Annotator)
  • D012380: Role (Publication, NCBO Annotator)
  • GO:0031099: regeneration (Publication, NCBO Annotator)
  • D055371: Acute Lung Injury (Publication, NCBO Annotator)
  • MA:0000415: lung (Publication, NCBO Annotator)
  • D002477: Cells (Publication, NCBO Annotator)
  • D007249: Inflammation (Publication, NCBO Annotator)
  • D008264: Macrophages (Publication, NCBO Annotator)
  • D008171: Lung Diseases (Publication, NCBO Annotator)
  • D004798: Enzymes (Publication, NCBO Annotator)
  • GO:0005623: cell (Publication, NCBO Annotator)
  • D007854: Lead (Publication, NCBO Annotator)
  • MP:0002169: no abnormal phenotype detected (Publication, NCBO Annotator)
  • D008214: Lymphocytes (Publication, NCBO Annotator)
  • D055370: Lung Injury (Publication, NCBO Annotator)
  • GO:0016265: death (Publication, NCBO Annotator)
  • D014024: Tissues (Publication, NCBO Annotator)
  • D018496: Hyperoxia (Publication, NCBO Annotator)
  • MP:0002319: hyperoxia (Publication, NCBO Annotator)

1 GeneSets from this Publication:

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Expand Tier II Mouse 542 Genes GS136022: hyperoxia susceptibility locus 1 (Hsl1, Published QTL Chr 2)