Induction of indoleamine 2,3-dioxygenase expression via heme oxygenase-1-dependant pathway during murine dendritic...

Heme oxygenase (HO)-1 is expressed in a variety of conditions involved in the regulation of immune responses. In this study, we examined the role of HO-1 in dendritic cell (DC) maturation and expression of indoleamine 2,3-dioxygenase (IDO), a key enzyme that catalyzes the initial, rate-limiting step in tryptophan degradation. IDO deficiency led to diminished phenotypic and functional maturation of DCs in vitro and in vivo. IDO expression and DC maturation was abrogated by the HO inhibitor zinc protoporphrin, but increased by hemin, a potent inducer of HO-1. Moreover, LPS-induced HO-1 expression was mediated by an NF-kappaB-dependent pathway. Our findings provide additional insight into the immunological functions of IDO and HO-1, and suggest possible therapeutic adjuvants for the treatment of DC-related acute and chronic diseases.