Regulation of IL-1β-induced GM-CSF production in human airway smooth muscle cells by carbon monoxide

Ruiping Song, Wen Ning, Fang Liu, Bill T. Ameredes, William J. Calhoun, Leo E. Otterbein, Augustine M.K. Choi

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Asthma, a chronic inflammatory disease of the airways, involves the increased expression of inflammatory mediators, including granulocyte-monocyte colony-stimulating factor (GM-CSF). Heme oxygenase-1 (HO-1), a stress-response protein, confers protection against oxidative stress. We hypothesized that carbon monoxide (CO), a byproduct of HO-1-dependent heme catabolism, regulates GM-CSF synthesis in human airway smooth muscle cells (HASMC). IL-1β treatment induced a time-dependent induction of GM-CSF in HASMC. Furthermore, IL-1β stimulated the major MAPK pathways, including ERK1/ERK2, JNK, and p38 MAPK. Exposure of HASMC to CO at low concentration (250 ppm) markedly inhibited IL-1β-induced GM-CSF synthesis (>90%) compared with air-treated controls. CO treatment inhibited IL-1β-induced ERK1/2 activation but did not inhibit JNK and p38 MAPK. Furthermore, CO increased cGMP levels in HASMC. Inhibition of guanylate cyclase by IH-[1,2,4] oxadiazolo[4,3-alquinoxalin-1-1 (ODQ) abolished the inhibitory effects of CO on GM-CSF synthesis and ERK1/2 activation. Collectively, these data demonstrate that the inhibitory effect of CO on GM-CSF synthesis depends on ERK1/2 MAPK and guanylate cyclase/cGMP-dependent pathways.

Original languageEnglish (US)
Pages (from-to)L50-L56
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number1 28-1
StatePublished - Jan 1 2003
Externally publishedYes


  • Cyclic guanosine monophosphate
  • Granulocyte-monocyte colony-stimulating factor
  • Mitogen activated protein kinase interleukin-1β

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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