title: Indoleamine 2,3-dioxygenase inhibition alters the non-coding RNA transcriptome following renal ischemia-reperfusion injury.
abstract: BACKGROUND
  Indoleamine 2,3 dioxygenase (IDO) degrades the essential amino acid tryptophan and has been shown to minimize rejection in animal models of renal transplantation. Ischemia-reperfusion injury (IRI) is unavoidable in renal transplantation and correlates with shorter graft survival times. Despite its favorable effects on rejection, there is evidence that IDO may facilitate renal IRI. Differentiating the negative impact of IDO on IRI from its pro-tolerant effects in allograft rejection is of clinical relevance. In these studies we hypothesized that constitutive IDO activity may influence renal genes associated with recovery from IRI, and that IDO inhibition may unmask these effects.
  
  
  METHODS
  We examined the renal transcriptome in a rat model of IRI with and without IDO inhibition with 1-methyl-d-tryptophan (1-MT), and assessed for alterations in the gene expression signature.
  
  
  RESULTS
  These studies demonstrated that during recovery from renal IRI, pre-treatment with 1-MT alleviated alterations in 105 coding sequences associated with IRI, and in turn triggered new changes in 66 non-coding transcripts, the majority of which were represented by small nucleolar RNA.
  
  
  CONCLUSIONS
  These results suggest a biologic role for non-coding, IDO-dependent genes in regulating the early response to IRI.
authors.affiliation: Department of Surgery, Georgia Regents University, Augusta, GA, United States.
authors.forename: Todd D
authors.initials: TD
authors.lastname: Merchen
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, United States.
authors.forename: Erika I
authors.initials: EI
authors.lastname: Boesen
authors.affiliation: Department of Medicine, Georgia Regents University Augusta, GA, United States.
authors.forename: John R
authors.initials: JR
authors.lastname: Gardner
authors.affiliation: Immunotherapy Center, Georgia Regents University Augusta, GA, United States.
authors.forename: Rachel
authors.initials: R
authors.lastname: Harbarger
authors.affiliation: Genomics Core, Comprehensive Cancer Center, Georgia Regents UniversityAugusta, GA, United States.
authors.forename: Eiko
authors.initials: E
authors.lastname: Kitamura
authors.affiliation: Immunotherapy Center, Georgia Regents University Augusta, GA, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mellor
authors.affiliation: Department of Medicine, Georgia Regents University Augusta, GA, United States.
authors.forename: David M
authors.initials: DM
authors.lastname: Pollock
authors.affiliation: Department of Surgery, Georgia Regents University, Augusta, GA, United States.
authors.forename: Arina
authors.initials: A
authors.lastname: Ghaffari
authors.affiliation: Department of Medicine, Georgia Regents University Augusta, GA, United States; Center for Biotechnology and Genomic Medicine, Georgia Regents UniversityAugusta, GA, United States; Department of Biostatistics, Georgia Regents University, Augusta, GA, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Podolsky
authors.affiliation: Department of Medicine, Georgia Regents University Augusta, GA, United States; Department of Medicine Georgia Regents University, Charlie Norwood VAMC, Augusta, GA, United States. Electronic address: nnahman@gru.edu.
authors.forename: N Stanley
authors.initials: NS
authors.lastname: Nahman
mesh_terms: D058186:Acute Kidney Injury / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000188:drug therapy; D006085:Graft Survival; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors*; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D022661:RNA, Untranslated / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D022661:RNA, Untranslated; C028129:tryptophan methyl ester; D014364:Tryptophan
keywords: Allograft tolerance; DNA microarray; Ischemic-reperfusion; Non-coding RNA transcriptome; Transplantation; Tryptophan