Abstract
Increasing evidence shows that oxidative stress plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of the human disease, multiple sclerosis (MS). Heme oxygenase-1 (HO-1) is a heat shock protein induced by oxidative stress. HO-1 metabolizes heme to the antioxidant bilirubin and carbon monoxide, and represents a powerful endogenous defensive mechanism against free radicals in many diseases. However, the role of this important enzyme in EAE remains unknown. In this study, we showed high expression of HO-1 in lesions of EAE, and demonstrated that hemin, an inducer of HO-1, inhibited EAE effectively. In contrast, tin mesoporphyrin, an inhibitor of HO-1, markedly exacerbated EAE. Our results suggest that endogenous HO-1 plays an important protective role in EAE, and that targeted induction of HO-1 overexpression may represent a new therapy for the treatment of multiple sclerosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Encephalomyelitis, Autoimmune, Experimental / drug therapy
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Encephalomyelitis, Autoimmune, Experimental / enzymology*
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Encephalomyelitis, Autoimmune, Experimental / physiopathology
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Enzyme Inhibitors / pharmacology
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Heme Oxygenase (Decyclizing) / drug effects
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Heme Oxygenase (Decyclizing) / metabolism*
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Heme Oxygenase-1
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Hemin / pharmacology
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Immunohistochemistry
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Lymph Nodes / cytology
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Lymph Nodes / drug effects
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Lymph Nodes / enzymology
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Macrophages / cytology
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Macrophages / drug effects
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Macrophages / enzymology
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Male
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Metalloporphyrins / pharmacology
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Multiple Sclerosis / drug therapy
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Multiple Sclerosis / enzymology*
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Multiple Sclerosis / physiopathology
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Neuroprotective Agents / pharmacology
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Oxidative Stress / drug effects
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Oxidative Stress / physiology*
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Rats
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Rats, Inbred Lew
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Spinal Cord / drug effects
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Spinal Cord / enzymology
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Spinal Cord / physiopathology
Substances
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Enzyme Inhibitors
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Metalloporphyrins
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Neuroprotective Agents
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tin mesoporphyrin
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Hemin
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Heme Oxygenase (Decyclizing)
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Heme Oxygenase-1