Regulation of indoleamine 2,3 dioxygenase and its role in a porcine model of acute kidney allograft rejection

Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research
Youli WangN Stanley Nahman

Abstract

In kidney transplantation acute allograft rejection is the most common cause of late allograft loss. Changes in indoleamine 2,3 dioxygenase (IDO) activity, which catabolizes the degradation of tryptophan to kynurenine, may predict rejection. However, exogenous IDO is immunosuppressive in rodent kidney transplantation. Thus, the increase in IDO activity observed in acute allograft rejection is insufficient to prevent rejection. To address this question, we assessed the regulation of IDO and its role in acute rejection in a porcine model of kidney transplant. In tissue samples from rejecting kidney allografts, we showed a 13-fold increase in IDO gene transcription and 20-fold increase in IDO enzyme activity when compared with autotransplanted kidneys. Allografts also demonstrated an over fourfold increase in tissue interferon (IFN)-γ, with marked increases in tumor necrosis factor (TNF)-α, TNF-β and interleukin 1β. Gene transcription and protein levels of kynurenine 3-monooxygenase (KMO) were decreased. KMO generates the immunosuppressive kynurenine, 3-hydroxykynurenine. The results of these studies demonstrate a clear association between rejection and increased allograft IDO expression, likely driven in part by IFN-γ and facilit...Continue Reading

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Citations

Dec 18, 2019·Annual Review of Animal Biosciences·Sabine E HammerJoan K Lunney
Jun 21, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Olga TroitskayaOlga Koval
Mar 7, 2021·International Journal of Molecular Sciences·Ruta ZulpaitePeter Schemmer

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