Heme oxygenase–1 and carbon monoxide suppress autoimmune neuroinflammation
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
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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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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