Indoleamine 2,3-dioxygenase expression promotes renal ischemia-reperfusion injury
| Autor: | Anthony M. Jevnikar, Hongtao Sun, Kanishka Mohib, Qiunong Guan, Andrew L. Mellor, Shuang Wang, Caigan Du |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Physiology Kidney urologic and male genital diseases Mice chemistry.chemical_compound Downregulation and upregulation Animals Indoleamine-Pyrrole 2 3 -Dioxygenase Medicine Indoleamine 2 3-dioxygenase Mice Knockout business.industry Tryptophan Epithelial Cells Articles medicine.disease Epithelium In vitro Up-Regulation Mice Inbred C57BL Kidney Tubules medicine.anatomical_structure chemistry Apoptosis Reperfusion Injury Immunology Cancer research Kidney Diseases business Reperfusion injury Kynurenine |
| Zdroj: | American Journal of Physiology-Renal Physiology. 295:F226-F234 |
| ISSN: | 1522-1466 1931-857X |
| Popis: | 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 micromol/l, n = 11) compared with mice treated with 1-methyl-D-tryptophan, a specific inhibitor of IDO (33.7 +/- 8.7 micromol/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 micromol/l, n = 6) following IRI compared with wild-type mice (123 +/- 30 micromol/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. |
| Databáze: | OpenAIRE |
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