Back to Search
Start Over
Regulation of indoleamine 2,3 dioxygenase and its role in a porcine model of acute kidney allograft rejection.
- Source :
-
Journal of investigative medicine : the official publication of the American Federation for Clinical Research [J Investig Med] 2018 Dec; Vol. 66 (8), pp. 1109-1117. Date of Electronic Publication: 2018 Jul 12. - Publication Year :
- 2018
-
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 facilitated by other cytokines of the allogeneic response. Moreover, the loss of downstream enzymatic activity in the IDO metabolic pathway may suggest novel mechanisms for the perpetuation of rejection.<br />Competing Interests: Competing interests: None declared.<br /> (© American Federation for Medical Research 2018. No commercial re-use. See rights and permissions. Published by BMJ.)
- Subjects :
- Animals
Creatinine blood
Cytokines genetics
Cytokines metabolism
Disease Models, Animal
Female
Gene Expression Regulation, Enzymologic
Graft Rejection blood
Indoleamine-Pyrrole 2,3,-Dioxygenase genetics
Kidney pathology
Kynurenine metabolism
Swine
Transcription, Genetic
Transplantation, Homologous
Allografts transplantation
Graft Rejection enzymology
Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism
Kidney Transplantation adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1708-8267
- Volume :
- 66
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of investigative medicine : the official publication of the American Federation for Clinical Research
- Publication Type :
- Academic Journal
- Accession number :
- 30006478
- Full Text :
- https://doi.org/10.1136/jim-2018-000742