Deficiency in the c-Jun NH2-terminal kinase signaling pathway confers susceptibility to hyperoxic lung injury in mice

Danielle Morse, Leo E. Otterbein, Simon Watkins, Sean Alber, Zhihong Zhou, Richard A. Flavell, Roger J. Davis, Augustine M.K. Choi

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Hyperoxia generates an oxidative stress in the mouse lung, which activates the major stress-inducible kinase pathways, including c-Jun NH2-terminal kinase (JNK). We examined the effect of Jnk1 gene deletion on in vivo responses to hyperoxia in mice. The survival of Jnk1-/- mice was reduced relative to wild-type mice after exposure to continuous hyperoxia. Jnk1-/- mice displayed higher protein concentration in bronchoalveolar lavage (BAL) fluid and increased expression of heme oxygenase-1, a stress-inducible gene, after 65 h of hyperoxia. Contrary to other markers of injury, the leukocyte count in BAL fluid of Jnk1-/- mice was markedly diminished relative to that of wild-type mice. The decrease in BAL leukocyte count was not associated with any decrease in lung myeloperoxidase activity at baseline or after hyperoxia treatment. Pretreatment with inhaled lipopolysaccharide increased BAL neutrophil content and extended hyperoxia survival time to a similar extent in Jnk1-/- and wild-type mice. Associated with increased mortality, Jnk1-/- mice had increased pulmonary epithelial cell apoptosis after exposure to hyperoxia compared with wild-type mice. These results indicate that JNK pathways participate in adaptive responses to hyperoxia in mice.

Original languageEnglish (US)
Pages (from-to)L250-L257
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume285
Issue number1 29-1
DOIs
StatePublished - Jul 1 2003

Keywords

  • Apoptosis
  • Hyperoxia
  • Mitogen-activated protein kinase
  • Oxidative stress
  • Oxygen toxicity
  • Stress response

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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