Heme Oxygenase-1 and Carbon Monoxide Suppress Autoimmune Neuroinflammation.
From: Instituto Gulbenkian de Ciência, Oeiras, Portugal. Departamento de Imunologia, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.
The Journal of clinical investigation
- Publish Date: Feb 2007
- ISSN: 0021-9738
- Volume: 117
- Issue: 2
- Pages: 438-47
- Medium: Print
- Language: English
- Citation (JAMA): Chora Angelo A, Fontoura Paulo, Cunha Andreia, et al. Heme Oxygenase-1 and Carbon Monoxide Suppress Autoimmune Neuroinflammation.. J. Clin. Invest. Feb 2007;117:438-47
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.
Mesh Headings (Keywords): Animals, Antigen-Presenting Cells, Autoimmunity, Carbon Monoxide, Encephalomyelitis, Autoimmune, Experimental, Enzyme Induction, Heme Oxygenase-1, Mice, Mice, Inbred C57BL, Mice, Knockout, T-Lymphocyte Subsets
Check for Full Text / PubMed Unique Identifier (PMID): 17256058
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