CCAAT/enhancer-binding protein mediates carbon monoxide-induced suppression of cyclooxygenase-2

Gee Young Suh, Yang Jin, Ae Kyung Yi, Xiao Mei Wang, Augustine M.K. Choi

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

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 m 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 E2 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 E2 secretion (P < 0.05). CO also decreased LPS-induced CCAAT/enhancer-binding protein (C/EBP) β and δ 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.

Original languageEnglish (US)
Pages (from-to)220-226
Number of pages7
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume35
Issue number2
DOIs
StatePublished - Aug 2006

Keywords

  • Heme oxygenase
  • Lipopolysaccharides
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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