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

Kanishka Mohib, Shuang Wang, Qiunong Guan, Andrew L. Mellor, Hongtao Sun, Caigan Du, Anthony M. Jevnikar

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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-γ and TNF-α 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume295
Issue number1
DOIs
StatePublished - Jul 1 2008

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Reperfusion Injury
Kidney
Reperfusion
Creatinine
Epithelial Cells
Kynurenine
Wounds and Injuries
Serum
Inbred C57BL Mouse
Constriction
Tryptophan
Up-Regulation
Ischemia

Keywords

  • Apoptosis
  • Renal function
  • Tubular epithelial cell

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Indoleamine 2,3-dioxygenase expression promotes renal ischemia-reperfusion injury. / Mohib, Kanishka; Wang, Shuang; Guan, Qiunong; Mellor, Andrew L.; Sun, Hongtao; Du, Caigan; Jevnikar, Anthony M.

In: American Journal of Physiology - Renal Physiology, Vol. 295, No. 1, 01.07.2008.

Research output: Contribution to journalArticle

Mohib, Kanishka ; Wang, Shuang ; Guan, Qiunong ; Mellor, Andrew L. ; Sun, Hongtao ; Du, Caigan ; Jevnikar, Anthony M. / Indoleamine 2,3-dioxygenase expression promotes renal ischemia-reperfusion injury. In: American Journal of Physiology - Renal Physiology. 2008 ; Vol. 295, No. 1.
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