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This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/F226    most recent 00567.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mohib, K. Articles by Jevnikar, A. M. Search for Related Content PubMed PubMed Citation Articles by Mohib, K. Articles by Jevnikar, A. M.

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

¹Departments of Medicine and Microbiology and Immunology, University of Western Ontario, and ²Robarts Research Institute, London, Ontario; ³Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia; ⁴Department of Medicine, Medical College of Georgia, Augusta, Georgia; ⁵Lawson Health Research Institute, London, Ontario; and ⁶Multi-Organ Transplant Program, London Health Sciences Center, London, Ontario, Canada

Submitted 28 November 2007 ; accepted in final form 12 May 2008

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- and TNF- 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°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 µmol/l, n = 11) compared with mice treated with 1-methyl-D-tryptophan, a specific inhibitor of IDO (33.7 ± 8.7 µmol/l, 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 µmol/l, n = 6) following IRI compared with wild-type mice (123 ± 30 µmol/l, n = 9, P = 0.008). Our data suggest that attenuation of IDO 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

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