MKK3 mitogen-activated protein kinase pathway mediates carbon monoxide-induced protection against oxidant-induced lung injury. Academic Article uri icon

Overview

MeSH

  • Animals
  • Carboxyhemoglobin
  • Cells, Cultured
  • Cytokines
  • Enzyme Activation
  • Hyperoxia
  • Inflammation Mediators
  • Lung
  • MAP Kinase Kinase 3
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases
  • Neutrophil Infiltration
  • Pneumonia
  • Survival Analysis
  • p38 Mitogen-Activated Protein Kinases

MeSH Major

  • Carbon Monoxide
  • Cytoprotection
  • Lung Diseases
  • Mitogen-Activated Protein Kinase Kinases
  • Oxidants
  • Protein-Tyrosine Kinases

abstract

  • The stress-inducible gene heme oxygenase (HO-1) has previously been shown to provide cytoprotection against oxidative stress. The mechanism(s) by which HO-1 provides this cytoprotection is poorly understood. We demonstrate here that carbon monoxide (CO), a byproduct released during the degradation of heme by HO, plays a major role in mediating the cytoprotection against oxidant-induced lung injury. We show in vitro that CO protects cultured epithelial cells from hyperoxic damage. By using dominant negative mutants and mice deficient in the genes for the various MAP kinases, we demonstrate that the cytoprotective effects of CO are mediated by selective activation of the MKK3/p38 beta protein MAP kinase pathway. In vivo, our experiments demonstrate that CO at a low concentration protects the lungs, extends the survival of the animals, and exerts potent anti-inflammatory effects with reduced inflammatory cell influx into the lungs and marked attenuation in the expression of pro-inflammatory cytokines.

publication date

  • December 2003

has subject area

  • Animals
  • Carbon Monoxide
  • Carboxyhemoglobin
  • Cells, Cultured
  • Cytokines
  • Cytoprotection
  • Enzyme Activation
  • Hyperoxia
  • Inflammation Mediators
  • Lung
  • Lung Diseases
  • MAP Kinase Kinase 3
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase Kinases
  • Mitogen-Activated Protein Kinases
  • Neutrophil Infiltration
  • Oxidants
  • Pneumonia
  • Protein-Tyrosine Kinases
  • Survival Analysis
  • p38 Mitogen-Activated Protein Kinases

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1892354

Digital Object Identifier (DOI)

  • 10.1016/S0002-9440(10)63610-3

PubMed ID

  • 14633627

Additional Document Info

start page

  • 2555

end page

  • 2563

volume

  • 163

number

  • 6