The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Heme oxygenase–1 and carbon monoxide suppress autoimmune neuroinflammation
Open accessAbstract
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.
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Cited by
Mechanisms of neurodegeneration and axonal dysfunction in multiple sclerosis
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Metadata
- Authors
- Chora, Â. A., Fontoura, P., Cunha, A., Pais, T. F., Cardoso, S., Ho, P. P., Lee, L. Y., Sobel, R. A., Steinman, L., & Soares, M. P.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-02-01
- Volume
- 117
- Issue
- 2
- Pages
- 438-447
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W1965109486
- Cited by
- 306
- References
- 56
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Chora, Â. A., Fontoura, P., Cunha, A., Pais, T. F., Cardoso, S., Ho, P. P., Lee, L. Y., Sobel, R. A., Steinman, L., & Soares, M. P. (2007). Heme oxygenase–1 and carbon monoxide suppress autoimmune neuroinflammation. Journal of Clinical Investigation. https://doi.org/10.1172/jci28844
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