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Heme oxygenase–1 and carbon monoxide suppress autoimmune neuroinflammation
Ângelo A. Chora, … , Lawrence Steinman, Miguel P. Soares
Ângelo A. Chora, … , Lawrence Steinman, Miguel P. Soares
Published February 1, 2007
Citation Information: J Clin Invest. 2007;117(2):438-447. https://doi.org/10.1172/JCI28844.
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Research Article Autoimmunity

Heme oxygenase–1 and carbon monoxide suppress autoimmune neuroinflammation

Abstract

Heme oxygenase–1 (HO-1, encoded by HMOX1) dampens inflammatory reactions via the catabolism of heme into CO, Fe, and biliverdin. We report that expression of HO-1 dictates the pathologic outcome of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). Induction of EAE in Hmox1–/– C57BL/6 mice led to enhanced CNS demyelination, paralysis, and mortality, as compared with Hmox1+/+ mice. Induction of HO-1 by cobalt protoporphyrin IX (CoPPIX) administration after EAE onset reversed paralysis in C57BL/6 and SJL/J mice and disease relapse in SJL/J mice. These effects were not observed using zinc protoporphyrin IX, which does not induce HO-1. CoPPIX protection was abrogated in Hmox1–/– C57BL/6 mice, indicating that CoPPIX acts via HO-1 to suppress EAE progression. The protective effect of HO-1 was associated with inhibition of MHC class II expression by APCs and inhibition of Th and CD8 T cell accumulation, proliferation, and effector function within the CNS. Exogenous CO mimicked these effects, suggesting that CO contributes to the protective action of HO-1. In conclusion, HO-1 or exposure to its end product CO counters autoimmune neuroinflammation and thus might be used therapeutically to treat MS.

Authors

Ângelo A. Chora, Paulo Fontoura, Andreia Cunha, Teresa F. Pais, Sílvia Cardoso, Peggy P. Ho, Lowen Y. Lee, Raymond A. Sobel, Lawrence Steinman, Miguel P. Soares

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Another target for suppresion of MS

Submitter: Kenneth A Hoekstra | khoekstra@wschiro.edu

Western States Chiropractic College

Published April 24, 2007

In the article by Chora et al. (1) the authors describe an exciting research project which examined the suppression of deleterious inflammatory response by inducible heme oxygenase (HO-1)in a mouse model of autoimmune encephalomyelitis (an animal model used to study multiple sclerosis). Although HO-1 has been identified in many neuroinflammatory disorders, the use of modulating HO-1 to aid in suppression of MS is an unique concept. A recent study has shown that HO-1 relocates to the nucleus of cells, activating transcription factors which may be important in the cytoprotection of cells against oxidative stress (2). This may be an important intervention step to explore in the suppression and progression of MS.
1. Chora AA, Fontoura P, Cunha A, Pais TF, Cardoso S, Ho PP, Lee LY, Sobel RA, Steinman L, Soares MP. Heme oxygenase–1 and carbon monoxide suppress autoimmune neuroinflammation. J. Clin. Invest. 2007; 117: 438-447.
2. Lin Q, Weis S, Yang G, Weng YH, Helston R, Rish K, Smith A, Bordner J, Polte T, Gaunitz F, Dennery PA. Heme oxygenase-1 protein localizes to the nucleus and activates transcription factors important in oxidative stress. J Biol Chem. 2007 Apr 12.

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