Indoleamine 2,3-dioxygenase expression promotes renal ischemia-reperfusion injury

Indoleamine 2,3-dioxygenase (IDO) catabolizes tryptophan to N-formyl kynurenine and has a proapoptotic role in renal tubular epithelial cells (TEC) in response to IFN-[gamma] and TNF-[alpha] in vitro. TEC produce abundant amounts of IDO in vitro in response to inflammation but a pathological role for IDO in renal injury remains unknown. We investigated the role of IDO in a mouse model of renal ischemia-reperfusion injury (IRI). IRI was induced by clamping the renal pedicle of C57BL/6 mice for 45 min at 32[degrees]C. Here, we demonstrate upregulation of IDO in renal tissue at 2 h after reperfusion which reached maximal levels at 24 h. Inhibition of IDO following IRI prevented the increase in serum creatinine observed in vehicle-treated mice (86.4 + 25 [micro]mol/1, n = 11) compared with mice treated with 1-methyl-o-tryptophan, a specific inhibitor of IDO (33.7 [+ or -] 8.7 [micro]mol/1, n = 10, P = 0.031). The role of IDO in renal IRI was further supported by results in IDO-KO mice which maintained normal serum creatinine levels (32.5 + 2.0 [micro]mol/1, n = 6) following IRI compared with wild-type mice (123 [+ or -] 30 [micro]mol/l, n = 9, P = 0.008). Our data suggest that attenuation of 1DO expression within the kidney may represent a novel strategy to reduce renal injury as a result of ischemia reperfusion. tubular epithelial cell; apoptosis; renal function