Steroid regulation: An overlooked aspect of tolerance and chronic rejection in kidney transplantation.

Autor: Christakoudi S; MRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK; Biostatistics and Health Informatics Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London SE5 8AF, UK. Electronic address: s.christakoudi@imperial.ac.uk., Runglall M; NIHR Biomedical Research Centre at Guy's & St Thomas' NHS Foundation Trust and King's College London, Great Maze Pond, London SE1 9RT, UK., Mobillo P; MRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK., Rebollo-Mesa I; MRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK; Biostatistics and Health Informatics Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London SE5 8AF, UK., Tsui TL; MRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK; Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London SE1 9RT, UK., Nova-Lamperti E; MRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK., Norris S; MRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK., Kamra Y; MRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK., Hilton R; Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London SE1 9RT, UK., Bhandari S; Hull and East Yorkshire Hospitals NHS Trust, Anlaby Rd, Hull HU3 2JZ, UK., Baker R; St James's University Hospital, Beckett St, Leeds LS9 7TF, UK., Berglund D; Department of Immunology, Genetics and Pathology, Uppsala University, Rudbecklaboratoriet, 751 85 Uppsala, Sweden., Carr S; Leicester General Hospital, Gwendolen Rd, Leicester LE5 4PW, UK., Game D; Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London SE1 9RT, UK., Griffin S; Cardiff and Vale University Health Board, Cardiff CF14 4XW, UK., Kalra PA; Salford Royal NHS Foundation Trust, Stott Ln, Salford M6 8HD, UK., Lewis R; Queen Alexandra Hospital, Southwick Hill Rd, Cosham, Portsmouth PO6 3LY, UK., Mark PB; University of Glasgow, University Avenue, Glasgow G12 8QQ, UK., Marks SD; Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond St, London WC1N 3JH, UK., Macphee I; St George's Hospital, Blackshaw Rd, London SW17 0QT, UK., McKane W; Northern General Hospital, Herries Rd, Sheffield S5 7AU, UK., Mohaupt MG; INSELSPITAL, Universitätsspital Department of Nephrology, Hypertension and Clinical Pharmacology, University Hospital, Freiburgstrasse 8, 3010 Bern, Switzerland., Pararajasingam R; Manchester Royal Infirmary, Oxford Rd, Manchester M13 9WL, UK., Kon SP; King's College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK., Serón D; Hospital Universitario Vall d'Hebrón, Passeig de la Vall d'Hebron, 119-129, 08035 Barcelona, Spain., Sinha M; Evelina London Children's Hospital, Westminster Bridge Rd, Lambeth, London SE1 7EH, UK., Tucker B; King's College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK., Viklický O; Transplantační laboratoř, Institut klinické a experimentální medicíny (IKEM), Vídeňská 1958/9, 140 21 Praha 4, Czech Republic., Lechler RI; MRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK; King's Health Partners, Guy's Hospital, London SE1 9RT, UK., Lord GM; MRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK; NIHR Biomedical Research Centre at Guy's & St Thomas' NHS Foundation Trust and King's College London, Great Maze Pond, London SE1 9RT, UK; Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London SE1 9RT, UK., Stahl D; Biostatistics and Health Informatics Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London SE5 8AF, UK., Hernandez-Fuentes MP; MRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK; King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
Jazyk: angličtina
Zdroj: Molecular and cellular endocrinology [Mol Cell Endocrinol] 2018 Sep 15; Vol. 473, pp. 205-216. Date of Electronic Publication: 2018 Feb 07.
DOI: 10.1016/j.mce.2018.01.021
Abstrakt: Steroid conversion (HSD11B1, HSD11B2, H6PD) and receptor genes (NR3C1, NR3C2) were examined in kidney-transplant recipients with "operational tolerance" and chronic rejection (CR), independently and within the context of 88 tolerance-associated genes. Associations with cellular types were explored. Peripheral whole-blood gene-expression levels (RT-qPCR-based) and cell counts were adjusted for immunosuppressant drug intake. Tolerant (n = 17), stable (n = 190) and CR patients (n = 37) were compared. Healthy controls (n = 14) were used as reference. The anti-inflammatory glucocorticoid receptor (NR3C1) and the cortisol-activating HSD11B1 and H6PD genes were up-regulated in CR and were lowest in tolerant patients. The pro-inflammatory mineralocorticoid gene (NR3C2) was downregulated in stable and CR patients. NR3C1 was associated with neutrophils and NR3C2 with T-cells. Steroid conversion and receptor genes, alone, enabled classification of tolerant patients and were major contributors to gene-expression signatures of both, tolerance and CR, alongside known tolerance-associated genes, revealing a key role of steroid regulation and response in kidney transplantation.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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