CCAAT/enhancer-binding protein mediates carbon monoxide-induced suppression of cyclooxygenase-2. Academic Article uri icon

Overview

MeSH

  • Animals
  • CCAAT-Enhancer-Binding Protein-delta
  • Cell Culture Techniques
  • Cell Line
  • Dinoprostone
  • Genes, Reporter
  • Heme Oxygenase-1
  • Isoenzymes
  • Lipopolysaccharides
  • Luciferases
  • Mice
  • Nitric Oxide Synthase Type II
  • Nitrites
  • Promoter Regions, Genetic
  • RNA, Messenger

MeSH Major

  • CCAAT-Enhancer-Binding Proteins
  • Carbon Monoxide
  • Cyclooxygenase 2
  • Gene Expression Regulation
  • Macrophages

abstract

  • Cyclooxygenase-2 (COX-2) is a key enzyme involved in the inflammatory process that is rapidly induced in macrophages in response to LPS. Carbon monoxide (CO), a byproduct of heme oxygnease-1, can suppress proinflammatory response in various in vitro and in vivo models of inflammation. This study was undertaken to examine whether CO can regulate (and if so, to delineate the mechanism by which CO regulates) LPS-induced COX-2 expression in macrophages. RAW 264.7 murine macrophages were stimulated with LPS (0-10 ng/ml) with or without CO (500 ppm). Northern and Western blot analysis was done. Progstaglandin E(2) and nitrite concentration was measured from cell culture supernatant. Electrophoretic mobility shift assay was performed to assess nuclear factor binding. CO downregulated LPS-induced COX-2 mRNA and protein expression. CO also inhibited LPS-induced prostaglandin E(2) secretion (P < 0.05). CO also decreased LPS-induced CCAAT/enhancer-binding protein (C/EBP) beta and delta protein expression in LPS-treated RAW 264.7 cells. Gel shift analysis revealed that CO treatment decreased LPS-induced activation of protein binding to C/EBP consensus oligonucleotides of murine cyclooxygenase-2 promoter. CO also decreased LPS-induced nitric oxide synthase-2 protein expression and nitrite production, and decreased LPS-induced activation of protein binding to C/EBP consensus oligonucleotides of murine nitric oxide synthase-2 promoter. CO may act as an important regulator of inflammation by virtue of its ability to regulate C/EBPs.

publication date

  • August 2006

has subject area

  • Animals
  • CCAAT-Enhancer-Binding Protein-delta
  • CCAAT-Enhancer-Binding Proteins
  • Carbon Monoxide
  • Cell Culture Techniques
  • Cell Line
  • Cyclooxygenase 2
  • Dinoprostone
  • Gene Expression Regulation
  • Genes, Reporter
  • Heme Oxygenase-1
  • Isoenzymes
  • Lipopolysaccharides
  • Luciferases
  • Macrophages
  • Mice
  • Nitric Oxide Synthase Type II
  • Nitrites
  • Promoter Regions, Genetic
  • RNA, Messenger

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2643257

Digital Object Identifier (DOI)

  • 10.1165/rcmb.2005-0154OC

PubMed ID

  • 16543610

Additional Document Info

start page

  • 220

end page

  • 226

volume

  • 35

number

  • 2