Heme oxygenase-1 plays an important protective role in experimental autoimmune encephalomyelitis.
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.
Liu
Y
Y
Brain Research Center, University of British Columbia, 2550 Willow Street, Vancouver, B.C. V5Z 3N9, Canada.
Zhu
B
B
Luo
L
L
Li
P
P
Paty
D W
DW
Cynader
M S
MS
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006427:Hemin / Q000494:pharmacology; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology
D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D018696:Neuroprotective Agents; C055421:tin mesoporphyrin; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1