炎症性疾患における Heme oxygenase-1 (HO-1) の発現

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Heme oxygenase(HO)-1 is an enzyme, an inducible form of HO, which catalyzes heme into carbon monoxide(CO), Fe2+, and biliverdin. CO suppresses apoptosis and macrophage activation, whereas biliverdin is converted into bilirubin, an antioxidant. Fe2+ stimulates the production of ferritin, a protective protein. Various noxious stimuli such as hypoxia or heavy metal loading induce expression of HO-1, which possesses cytoprotective effects mediated by the heme degradation products. Indeed, forced or chemically induced expression of HO-1 has beneficial effects on respiratory, inflammatory, renal diseases, and inflammatory disorders in animal models. On the other hand, HO-1 deficiency leads to systemic inflammation in mice and a patient. HO-1 is involved in pathogenesis of various diseases. Some of malignant tumors express abundant HO-1, resulting in suppressed apoptosis of tumor cells, whereas reduced expression of HO-1 is implicated in degenerative diseases such as Alzheimer dementia. Our preliminary results showed increased expression of HO-1 in joint lesions of rheumatoid arthritis and circulating leukocytes from patients with adult-onset Stills disease and hemophagocytic syndrome, though the role of HO-1 remains unknown in these diseases. Excessively expressed HO-1 appears toxic in some conditions. HO-1 induction by auranofin and statins has been shown to contribute to the pharmacological effects at least in part. To optimize HO-1 expression may lead to development of novel therapeutic strategies in various diseases including inflammatory disorders.
日本炎症・再生医学会の論文
2005-09-25

炎症性疾患における Heme oxygenase-1 (HO-1) の発現

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