Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 17 1 2018 02 26 56 67 EN Theodoros Eleftheriadis Department of Nephrology, Medical School, University of Thessaly, Larissa, Greece Georgios Pissas Department of Nephrology, Medical School, University of Thessaly, Larissa, Greece Vassilios Liakopoulos Department of Nephrology, Medical School, University of Thessaly, Larissa, Greece Ioannis Stefanidis Department of Nephrology, Medical School, University of Thessaly, Larissa, Greece 2017 05 06 2017 07 24 Indoleamine 2, 3-dioxygenase (IDO) suppresses T-cell function at least in part by altering cell metabolism. Hypoxia-inducible factor-1 (HIF-1) increases upon T-cell activation and alters cell metabolism favoring their differentiation to effector cells. The effect of IDO on HIF-1α expression and activity was evaluated. For this purpose, mixed lymphocyte reaction (MLR) was performed using the IDO inhibitor 1-DL-methyl-tryptophan and the p53 inhibitor pifithrin-α. L-tryptophan degradation and cell proliferation were assessed by enzyme-linked immunosorbent assay, whereas the expression of proteins of interest by western blotting. IDO inhibited cell proliferation, and in MLR-derived T-cells increased HIF-1α and p53, whereas it decreased c-Myc. Inhibition of p53 abrogated IDO-induced HIF-1α upregulation. IDO increased the p53 transcriptional targets p21 and TP53-induced glycolysis and apoptosis regulator. The transcriptional targets of both HIF-1α and c-Myc, hexokinase II and lactate dehydrogenase-A were decreased by IDO. Phosphorylated pyruvate dehydrogenase remained unaffected indicating that pyruvate dehydrogenase kinase, a transcriptional target of HIF-1α, is not affected by IDO. In human alloreactive T-cells, IDO up-regulates HIF-1α, by inducing p53 overexpression. However, HIF-1α remains transcriptionally inactive. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1454 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1454/814