Carbon monoxide modulates endotoxin-induced production of granulocyte macrophage colony-stimulating factor in macrophages. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cells, Cultured
  • Gene Expression
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • I-kappa B Proteins
  • Membrane Proteins
  • Mice
  • NF-KappaB Inhibitor alpha
  • NF-kappa B
  • Phosphorylation
  • Up-Regulation

MeSH Major

  • Carbon Monoxide
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Lipopolysaccharides
  • Macrophages, Peritoneal

abstract

  • The stress-inducible gene heme oxygenase-1 (HO-1) provides protection against oxidative stress. Although the mechanisms by which HO-1 exerts its cytoprotection are not clearly understood, it has been speculated that carbon monoxide (CO), a catalytic byproduct following heme catabolism by HO-1, may mediate cellular cytoprotection via its anti-inflammatory properties. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a potent cytokine generated in response to bacterial endotoxin (lipopolysaccharide [LPS]) to stimulate proliferation, maturation, and effector functions of leukocytes, contributing to the proinflammatory responses to LPS. We hypothesized that HO-1 and/or CO could regulate the expression and production of GM-CSF. HO-1 overexpression, as well as exposure to a low concentration of CO, inhibited LPS-induced GM-CSF production in macrophages. Furthermore, CO inhibited LPS-induced GM-CSF induction via inhibition in the activation of the transcription factor NF-kappaB. CO inhibited LPS-induced activation of NF-kappaB, which has been shown to regulate GM-CSF transcription, by preventing the phosphorylation and degradation of the regulatory subunit IkappaB-alpha. These data raise the intriguing possibility that CO at low concentrations may play an important role in inflammatory disease states and thus has potential therapeutic implications.

publication date

  • December 2002

has subject area

  • Animals
  • Carbon Monoxide
  • Cells, Cultured
  • Gene Expression
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • I-kappa B Proteins
  • Lipopolysaccharides
  • Macrophages, Peritoneal
  • Membrane Proteins
  • Mice
  • NF-KappaB Inhibitor alpha
  • NF-kappa B
  • Phosphorylation
  • Up-Regulation

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1165/rcmb.4816

PubMed ID

  • 12444034

Additional Document Info

start page

  • 739

end page

  • 745

volume

  • 27

number

  • 6