Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway.
Heme Oxygenase (Decyclizing)
MAP Kinase Kinase 3
Macrophage Inflammatory Proteins
Mice, Inbred C57BL
RNA Processing, Post-Transcriptional
Tumor Necrosis Factor-alpha
Anti-Inflammatory Agents, Non-Steroidal
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase Kinases
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.