[Heme oxygenase and its role in defense system; paradigm shift of anti-inflammatory therapy].

Heme oxygenase (HO) plays a central role in heme metabolism. At the same time, it protects cells from injury evoked by various oxidative stresses. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs. It is particularly important that in vivo HO-1 production is localized to selected cell types, e.g. renal tubular epithelium, reflecting the fact that HO-1 plays particularly important protective roles in these cells. In addition to renal epithelial cells and tissue macrophages, a minor subpopulation of circulating monocytes produced low, but significant levels of HO-1 and the number of these monocytes increased during episodes of acute inflammatory illnesses, indicating that monocytes play significant roles in controlling inflammation. On the other hand, excessive level of HO-1 induced by HO-1 gene transfection led to paradoxical susceptibility of the cells to oxidative injury. These results indicated that HO-1 expression is carefully controlled in vivo with regard to its location and the magnitude. Furthermore, it has been recently shown that HO-1 is involved in the immune regulation mediated by regulatory T cells. From these findings, it seems feasible to meticulously induce HO-1 protein in vivo as a novel therapeutic intervention to control various forms of inflammatory disorders.