Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cell Line
  • Cells, Cultured
  • Chemokine CCL4
  • Cyclic GMP
  • Enzyme Activation
  • Gene Expression
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Humans
  • Interferon-gamma
  • Interleukin-1
  • Interleukin-10
  • Lipopolysaccharides
  • MAP Kinase Kinase 3
  • Macrophage Inflammatory Proteins
  • Macrophages, Peritoneal
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogens
  • Nitric Oxide
  • RNA Processing, Post-Transcriptional
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha

MeSH Major

  • Anti-Inflammatory Agents, Non-Steroidal
  • Carbon Monoxide
  • MAP Kinase Signaling System
  • Mitogen-Activated Protein Kinase Kinases
  • Protein-Tyrosine Kinases

abstract

  • The stress-inducible protein heme oxygenase-1 provides protection against oxidative stress. The anti-inflammatory properties of heme oxygenase-1 may serve as a basis for this cytoprotection. We demonstrate here that carbon monoxide, a by-product of heme catabolism by heme oxygenase, mediates potent anti-inflammatory effects. Both in vivo and in vitro, carbon monoxide at low concentrations differentially and selectively inhibited the expression of lipopolysaccharide-induced pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and macrophage inflammatory protein-1beta and increased the lipopolysaccharide-induced expression of the anti-inflammatory cytokine interleukin-10. Carbon monoxide mediated these anti-inflammatory effects not through a guanylyl cyclase-cGMP or nitric oxide pathway, but instead through a pathway involving the mitogen-activated protein kinases. These data indicate the possibility that carbon monoxide may have an important protective function in inflammatory disease states and thus has potential therapeutic uses.

publication date

  • April 2000

has subject area

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal
  • Carbon Monoxide
  • Cell Line
  • Cells, Cultured
  • Chemokine CCL4
  • Cyclic GMP
  • Enzyme Activation
  • Gene Expression
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Humans
  • Interferon-gamma
  • Interleukin-1
  • Interleukin-10
  • Lipopolysaccharides
  • MAP Kinase Kinase 3
  • MAP Kinase Signaling System
  • Macrophage Inflammatory Proteins
  • Macrophages, Peritoneal
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase Kinases
  • Mitogens
  • Nitric Oxide
  • Protein-Tyrosine Kinases
  • RNA Processing, Post-Transcriptional
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1038/74680

PubMed ID

  • 10742149

Additional Document Info

start page

  • 422

end page

  • 428

volume

  • 6

number

  • 4