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Potential role of indoleamine 2,3-dioxygenase in primary biliary cirrhosis.

Asghar, Kashif, Brain, John, Palmer, Jeremy M, Douglass, Stephen, Naemi, Fatmah M A, O'Boyle, Graeme, Kirby, John and Ali, Simi (2017) Potential role of indoleamine 2,3-dioxygenase in primary biliary cirrhosis. Oncology letters, 14 (5). pp. 5497-5504. ISSN 1792-1074

Item Type: Article

Abstract

Indoleamine 2,3-dioxygenase (IDO)-induced immunosuppression can be clinically beneficial for autoimmune diseases. Primary biliary cirrhosis (PBC) is characterized by autoimmune lesions of intrahepatic bile duct epithelial cells that may lead to irreversible cirrhosis or hepatocellular carcinoma. The present study assessed the expression and function of IDO in a cell culture model and in PBC patients. IDO expression was monitored in a human immortalized but non-malignant biliary epithelial cell (iBEC) line. Increased expression of IDO1/2 was observed in the iBECs following stimulation with interferon-γ (IFN-γ). The induction of IDO was IFN-γ-dependent, but was independent of the transforming growth factor-β (TGF-β) pathway. IDO enzymatic activity was observed in the supernatant of iBECs following stimulation with IFN-γ using colorimetric assays. A total of 47 serum samples from PBC patients were used to examine IDO activity by high-performance liquid chromatography, with samples from 24 healthy volunteers used as controls. Patients with PBC exhibited an increased rate of tryptophan to kynurenine conversion (P>0.01). Liver sections from patients with PBC (n=5) and those of healthy controls (n=5) were used for immunohistochemical studies. IDO expression was observed in biliary epithelial cells and in hepatocytes of PBC patients. Finally, the effect of tryptophan metabolites on human cluster of differentiation (CD) 4 T cells in inducing polarization towards a regulatory T cell phenotype was examined. 3-Hydroxykynurenine significantly upregulated the fraction of CD4 cells expressing forkhead box p3 (Foxp3). The results of the present study suggest a therapeutic opportunity for the management of PBC and indicate that tryptophan catabolism could serve as a potential biomarker to monitor disease progression.

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Depositing User: Graeme O'Boyle

Identifiers

Item ID: 9295
Identification Number: https://doi.org/10.3892/ol.2017.6834
ISSN: 1792-1074
URI: http://sure.sunderland.ac.uk/id/eprint/9295
Official URL: https://www.spandidos-publications.com/10.3892/ol....

Users with ORCIDS

ORCID for Graeme O'Boyle: ORCID iD orcid.org/0000-0002-0472-8061

Catalogue record

Date Deposited: 09 May 2018 12:15
Last Modified: 18 Dec 2019 16:06

Contributors

Author: Graeme O'Boyle ORCID iD
Author: Kashif Asghar
Author: John Brain
Author: Jeremy M Palmer
Author: Stephen Douglass
Author: Fatmah M A Naemi
Author: John Kirby
Author: Simi Ali

University Divisions

Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Nursing and Health Sciences

Subjects

Sciences > Biomedical Sciences

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