Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway
Graduate School of Biomedical Sciences; Program in Molecular Medicine
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
Life Sciences | Medicine and Health Sciences
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.
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Citation: Nat Med. 2000 Apr;6(4):422-8. Link to article on publisher's site
DOI of Published Version
Otterbein, Leo E.; Bach, Fritz H.; Alam, Jawed; Soares, Miguel P.; Lu, Hong-Tao; Wysk, Mark Allen; Davis, Roger J.; Flavell, Richard A.; and Choi, Augustine M. K., "Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway" (2000). GSBS Student Publications. 925.