Heme Oxygenase-1 plays an important protective role in experimental autoimmune encephalomylitis

Increasing evidence shows that oxidative stress plays an important role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Heme oxygenase-1 (HO-1) is a heat shock protein induced by oxidative stress, and represents a powerful endogenous defensive mechanism against free radicals in many diseases. However, the role of this important enzyme in EAE remains unknown. The purpose of this thesis is to investigate the induction of HO-1 in EAE, and evaluate its effect on this disease. The expression of HO-1 in EAE was detected by Western blot analysis and immunohistochemistry. These studies revealed that HO-1 is strongly induced in EAE lesions, while none could be detected in the normal rat spinal cord. However, the level of HO-1 expression is different at various phases of EAE. The expression of HO-1 is weak at the onset of clinical signs. During the following days, HO-1 activity increases substantially as disease progresses, and reaches its maximum at the peak of clinical signs. Subsequently, I demonstrated that hemin, an inducer of HO-1, inhibited EAE effectively. In contrast, tin mesoporphyrin, an inhibitor of HO-1, markedly worsened EAE especially at the peak period of disease, correlating well with the level of HO-1 activity at this time. These data indicate that HO-1 plays an important protective role in EAE, and that targeted induction of HO-1 overexpression by pharmacological modulation may serve as a novel approach to therapeutic intervention in MS.Medicine, Faculty ofGraduat