Indoleamine 2,3-dioxygenase increases p53 levels in alloreactive human T cells, and both indoleamine 2,3-dioxygenase and p53 suppress glucose uptake, glycolysis and proliferation
| العنوان: | Indoleamine 2,3-dioxygenase increases p53 levels in alloreactive human T cells, and both indoleamine 2,3-dioxygenase and p53 suppress glucose uptake, glycolysis and proliferation |
|---|---|
| المؤلفون: | Theodoros Eleftheriadis, Georgios Pissas, Vassilios Liakopoulos, Aginor Spanoulis, Ioannis Stefanidis, Georgia Antoniadi |
| المصدر: | International Immunology. 26:673-684 |
| بيانات النشر: | Oxford University Press (OUP), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, T-Lymphocytes, Glucose uptake, Lymphocyte Activation, chemistry.chemical_compound, Immunology and Allergy, Glycolysis, Indoleamine 2,3-dioxygenase, Cells, Cultured, Glucose Transporter Type 1, Kinase, TOR Serine-Threonine Kinases, Intracellular Signaling Peptides and Proteins, Tryptophan, General Medicine, Middle Aged, Pifithrin, Healthy Volunteers, Cell biology, Isoenzymes, Female, Adult, medicine.medical_specialty, Immunology, Glucosephosphate Dehydrogenase, Mechanistic Target of Rapamycin Complex 1, Biology, Mitochondrial Proteins, Internal medicine, medicine, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase, Benzothiazoles, Lactic Acid, Cell Proliferation, Glutaminolysis, L-Lactate Dehydrogenase, Cell growth, Phosphoric Monoester Hydrolases, Enzyme Activation, Glucose, Endocrinology, chemistry, Anaerobic glycolysis, Multiprotein Complexes, Leukocytes, Mononuclear, Lactate Dehydrogenase 5, Lymphocyte Culture Test, Mixed, Tumor Suppressor Protein p53, Apoptosis Regulatory Proteins, Carrier Proteins, Molecular Chaperones, Toluene |
| الوصف: | Indoleamine 2,3-dioxygenase (IDO) suppresses adaptive immunity by inhibiting T-cell proliferation and altering glucose metabolism. The tumor suppressor p53 also alters these cellular processes with similar results. The effect of IDO on p53 and on glucose metabolism was evaluated in alloreactive T cells. Mixed-lymphocyte reactions (MLRs) were performed in the presence or not of the IDO inhibitor, 1-dl-methyl-tryptophan (1-MT) and/or the p53 inhibitor, pifithrin-α (PFT). Cell proliferation, glucose consumption and lactate production were assessed. 1-MT increased cell proliferation, glucose influx and lactate production, whereas PFT enhanced cell proliferation and glucose influx, leaving lactate production unaffected. In MLR-derived T cells, protein analysis revealed that IDO activated general control non-derepressible 2 kinase and induced p53, p-p53 (p53 phosphorylated at serine 15) and p21. In addition, both IDO and p53 decreased glucose transporter 1 and TP53-induced glycolysis and apoptosis regulator and increased synthesis of cytochrome c oxidase 2. IDO also reduced lactate dehydrogenase-A and glutaminase 2 levels, whereas p53 left them unaffected. Neither 1-MT nor PFT affected glucose-6-phosphate dehydrogenase. In conclusion, in alloreactive T cells, IDO increases p53 levels, and both IDO and p53 inhibit cell proliferation, glucose consumption and glycolysis. Lactate production and glutaminolysis are also suppressed by IDO, but not by p53. |
| تدمد: | 1460-2377 0953-8178 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5ccdc835a9cba63c91bb02ad2e6c32daTest https://doi.org/10.1093/intimm/dxu077Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5ccdc835a9cba63c91bb02ad2e6c32da |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602377 09538178 |
|---|