Carbon monoxide modulates endotoxin-induced production of granulocyte macrophage colony-stimulating factor in macrophages

Judit K. Sarady, Sherrie L. Otterbein, Fang Liu, Leo E. Otterbein, Augustine M.K. Choi

Research output: Contribution to journalArticle

116 Scopus citations

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 heine 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-κB. CO inhibited LPS-induced activation of NF-κB, which has been shown to regulate GM-CSF transcription, by preventing the phosphorylation and degradation of the regulatory subunit IκB-α. 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.

Original languageEnglish (US)
Pages (from-to)739-745
Number of pages7
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume27
Issue number6
DOIs
StatePublished - Dec 1 2002

ASJC Scopus subject areas

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

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