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Steroid regulation: An overlooked aspect of tolerance and chronic rejection in kidney transplantation
S. Christakoudi, M. Runglall, P. Mobillo, I. Rebollo-Mesa, TL. Tsui, E. Nova-Lamperti, S. Norris, Y. Kamra, R. Hilton, S. Bhandari, R. Baker, D. Berglund, S. Carr, D. Game, S. Griffin, PA. Kalra, R. Lewis, PB. Mark, SD. Marks, I. Macphee, W....
Jazyk angličtina Země Irsko
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
MR/J006742/1
Medical Research Council - United Kingdom
G0801537
Medical Research Council - United Kingdom
Department of Health - United Kingdom
- MeSH
- chronická nemoc MeSH
- imunologická tolerance * účinky léků genetika MeSH
- lidé MeSH
- multivariační analýza MeSH
- plocha pod křivkou MeSH
- počet buněk MeSH
- pravděpodobnost MeSH
- prednisolon aplikace a dávkování farmakologie MeSH
- protein - isoformy metabolismus MeSH
- receptory glukokortikoidů metabolismus MeSH
- regresní analýza MeSH
- regulace genové exprese účinky léků MeSH
- rejekce štěpu etiologie genetika imunologie MeSH
- steroidy farmakologie MeSH
- transplantace ledvin škodlivé účinky MeSH
- upregulace účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
Cardiff and Vale University Health Board Cardiff CF14 4XW UK
Evelina London Children's Hospital Westminster Bridge Rd Lambeth London SE1 7EH UK
Great Ormond Street Hospital for Children NHS Foundation Trust Great Ormond St London WC1N 3JH UK
Guy's and St Thomas' NHS Foundation Trust Great Maze Pond London SE1 9RT UK
Hospital Universitario Vall d'Hebrón Passeig de la Vall d'Hebron 119 129 08035 Barcelona Spain
Hull and East Yorkshire Hospitals NHS Trust Anlaby Rd Hull HU3 2JZ UK
King's College Hospital NHS Foundation Trust Denmark Hill London SE5 9RS UK
King's Health Partners Guy's Hospital London SE1 9RT UK
Leicester General Hospital Gwendolen Rd Leicester LE5 4PW UK
Manchester Royal Infirmary Oxford Rd Manchester M13 9WL UK
MRC Centre for Transplantation King's College London Great Maze Pond London SE1 9RT UK
Northern General Hospital Herries Rd Sheffield S5 7AU UK
Queen Alexandra Hospital Southwick Hill Rd Cosham Portsmouth PO6 3LY UK
Salford Royal NHS Foundation Trust Stott Ln Salford M6 8HD UK
St George's Hospital Blackshaw Rd London SW17 0QT UK
Citace poskytuje Crossref.org
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