Differential modulation by exogenous carbon monoxide of TNF-alpha stimulated mitogen-activated protein kinases in rat pulmonary artery endothelial cells. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cells, Cultured
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Kinetics
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Phosphorylation
  • Pulmonary Artery
  • Rats
  • Recombinant Proteins
  • Time Factors
  • Transfection

MeSH Major

  • Carbon Monoxide
  • Endothelium, Vascular
  • Mitogen-Activated Protein Kinases
  • Tumor Necrosis Factor-alpha

abstract

  • Heme oxygenase-1 (HO-1) is an enzyme that is highly inducible by various cellular stressors, especially oxidant injury. Our laboratory and others have demonstrated that induction of HO-1 exerts an antiinflammatory effect both in vitro and in vivo. We hypothesized that carbon monoxide (CO), a major catalytic byproduct of heme catalysis by HO-1, may mediate this antiinflammatory effect by modulating signal transduction pathways, in particular the mitogen-activated protein (MAP) kinase pathway. Confluent primary cultures of rat pulmonary artery endothelial cells (RPAEC) were treated with tumor necrosis factor-alpha (TNF-alpha; 50 ng/ml), and whole-cell extracts were assayed for phosphorylated ERK1/2, JNK1/2, and p38 MAP kinases. These three major MAP kinase pathways were activated by TNF-alpha in a time-dependent manner. RPAEC treated with TNF-alpha in the presence of a low concentration of CO (1%) exhibited marked attenuation of the phosphorylation of ERK1/2 MAP kinase when compared with cells treated with TNF-alpha alone. A similar effect was seen on the upstream MEK 1/2 kinase. Interestingly, CO (1%) accentuated TNF-alpha-induced phosphorylated p38 MAP kinase. These effects of exogenous CO on the ERK1/2 and p38 systems could be replicated by overexpression of HO-1 in RPAEC, using an adenoviral vector. As these MAP kinases are implicated in the regulation of various inflammatory molecules and adhesion molecules, our data provide a potential mechanism by which HO-1, acting via CO, may modulate the inflammatory response by differential activation of the MAP kinase pathway.

publication date

  • April 2002

has subject area

  • Animals
  • Carbon Monoxide
  • Cells, Cultured
  • Endothelium, Vascular
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Kinetics
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Phosphorylation
  • Pulmonary Artery
  • Rats
  • Recombinant Proteins
  • Time Factors
  • Transfection
  • Tumor Necrosis Factor-alpha

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1089/152308602753666299

PubMed ID

  • 12006175

Additional Document Info

start page

  • 241

end page

  • 248

volume

  • 4

number

  • 2