Carbon monoxide has anti-inflammatory effects involving the mitogen- activated protein kinase pathway

Leo E. Otterbein, Fritz H. Bach, Jawed Alam, Miguel Soares, Hong Tao Lu, Mark Wysk, Roger J. Davis, Richard A. Flavell, Augustine M.K. Choi

Research output: Contribution to journalArticlepeer-review

1709 Scopus citations

Abstract

The stress-inducible protein heme oxygenase-1 provides protection against oxidative stress. The anti-inflammatory properties of heme oxygenase- 1 may serve as a basis for this cytoprotection. We demonstrate here that carbon monoxide, a by-product of heme catabolism by heme oxygenase, mediates potent anti-inflammatory effects. Both in vivo and in vitro, carbon monoxide at low concentrations differentially and selectively inhibited the expression of lipopolysaccharide-induced pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-1β and increased the lipopolysaccharide-induced expression of the anti-inflammatory cytokine interleukin-10. Carbon monoxide mediated these anti-inflammatory effects not through a guanylyl cyclase-cGMP or nitric oxide pathway, but instead through a pathway involving the mitogen-activated protein kinases. These data indicate the possibility that carbon monoxide may have an important protective function in inflammatory disease states and thus has potential therapeutic uses.

Original languageEnglish (US)
Pages (from-to)422-428
Number of pages7
JournalNature Medicine
Volume6
Issue number4
DOIs
StatePublished - Apr 2000

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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