Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway
Graduate School of Biomedical Sciences; Program in Molecular Medicine
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.
DOI of Published Version
Nat Med. 2000 Apr;6(4):422-8. Link to article on publisher's site
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.