GSBS Student Publications

Title

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

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Molecular Medicine

Date

3-31-2000

Document Type

Article

Medical Subject Headings

Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbon Monoxide; Cell Line; Cells, Cultured; Chemokine CCL4; Cyclic GMP; Enzyme Activation; Gene Expression; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Humans; Interferon Type II; Interleukin-1; Interleukin-10; Lipopolysaccharides; MAP Kinase Kinase 3; *MAP Kinase Signaling System; Macrophage Inflammatory Proteins; Macrophages, Peritoneal; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitogen-Activated Protein Kinase Kinases; Mitogens; Nitric Oxide; Protein-Tyrosine Kinases; RNA Processing, Post-Transcriptional; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Disciplines

Life Sciences | Medicine and Health Sciences

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-alpha, interleukin-1beta, and macrophage inflammatory protein-1beta 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.

Rights and Permissions

Citation: Nat Med. 2000 Apr;6(4):422-8. Link to article on publisher's site

DOI of Published Version

10.1038/74680

Related Resources

Link to article in PubMed

Journal Title

Nature medicine

PubMed ID

10742149