dc.creator | Eleftheriadis T., Pissas G., Sounidaki M., Tsogka K., Antoniadis N., Antoniadi G., Liakopoulos V., Stefanidis I. | en |
dc.date.accessioned | 2023-01-31T07:37:22Z | |
dc.date.available | 2023-01-31T07:37:22Z | |
dc.date.issued | 2016 | |
dc.identifier | 10.3892/ijmm.2016.2750 | |
dc.identifier.issn | 11073756 | |
dc.identifier.uri | http://hdl.handle.net/11615/71364 | |
dc.description.abstract | Indoleamine 2,3-dioxygenase (IDO) is expressed in antigen presenting cells and by degrading L-tryptophan along the kynurenine pathway suppresses CD4+ T-cell proliferation, induces apoptosis and promotes differentiation towards a regulatory as opposed to an effector phenotype. Recent findings revealed that the above effects may be mediated through alterations in T-cell metabolism. In this study, the effect of IDO on fatty acid oxidation in CD4+ T-cells was evaluated in human mixed lymphocyte reactions (MLRs) using the IDO inhibitor, 1-DL-methyl-tryptophan. Protein analysis of CD4+ T-cells isolated from the MLR showed that L-tryptophan degradation acts by activating the general control non derepressible 2 kinase and aryl-hydrocarbon receptor in T-cells. In the absence of IDO inhibition, fatty acid oxidation increased along with increased activity of carnitine palmitoyltransferase I (CPT1), the latter due to the increased expression of CPT1 isoenzymes and alterations in acetyl-CoA carboxylase 2, the enzyme that controls CPT1 activity. Increased fatty acid oxidation due to the action of IDO was accompanied by an increased expression of forkhead box P3 (FoxP3) and a decreased expression of related orphan receptor t (RORt), the signature transcription factors of regulatory T-cells and T helper 17 cells, respectively. However, in MLR and in the presence of fatty acid in the culture medium, IDO did not inhibit proliferation. Additionally, fatty acid protected the CD4+ T-cells against apoptosis. Thus, IDO, by degrading L-tryptophan, enhances CPT1 activity and fatty acid oxidation, and exerts fatty aciddependent effects in human alloreactive CD4+ T-cells. | en |
dc.language.iso | en | en |
dc.source | International Journal of Molecular Medicine | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84992715387&doi=10.3892%2fijmm.2016.2750&partnerID=40&md5=3d8047dee227997884c7fdec17c6a68d | |
dc.subject | acetyl coenzyme A carboxylase | en |
dc.subject | acetyl coenzyme A carboxylase 2 | en |
dc.subject | aromatic hydrocarbon receptor | en |
dc.subject | carnitine palmitoyltransferase I | en |
dc.subject | fatty acid | en |
dc.subject | indoleamine 2,3 dioxygenase | en |
dc.subject | n methyltryptophan | en |
dc.subject | retinoid related orphan receptor gamma | en |
dc.subject | transcription factor FOXP3 | en |
dc.subject | tryptophan | en |
dc.subject | unclassified drug | en |
dc.subject | 1-methyltryptophan | en |
dc.subject | carnitine palmitoyltransferase | en |
dc.subject | EIF2AK1 protein, human | en |
dc.subject | eIF2alpha kinase, mouse | en |
dc.subject | fatty acid | en |
dc.subject | forkhead transcription factor | en |
dc.subject | FOXP3 protein, human | en |
dc.subject | indoleamine 2,3 dioxygenase | en |
dc.subject | protein kinase R | en |
dc.subject | protein serine threonine kinase | en |
dc.subject | retinoid related orphan receptor gamma | en |
dc.subject | tryptophan | en |
dc.subject | adult | en |
dc.subject | alloreactive T cell | en |
dc.subject | apoptosis | en |
dc.subject | Article | en |
dc.subject | CD4+ T lymphocyte | en |
dc.subject | controlled study | en |
dc.subject | enzymatic degradation | en |
dc.subject | enzyme activity | en |
dc.subject | fatty acid oxidation | en |
dc.subject | female | en |
dc.subject | human | en |
dc.subject | human cell | en |
dc.subject | lymphocyte proliferation | en |
dc.subject | male | en |
dc.subject | mixed lymphocyte reaction | en |
dc.subject | priority journal | en |
dc.subject | analogs and derivatives | en |
dc.subject | antagonists and inhibitors | en |
dc.subject | CD4+ T lymphocyte | en |
dc.subject | cell culture | en |
dc.subject | cytology | en |
dc.subject | drug effects | en |
dc.subject | lymphocyte activation | en |
dc.subject | metabolism | en |
dc.subject | mixed lymphocyte culture | en |
dc.subject | oxidation reduction reaction | en |
dc.subject | phosphorylation | en |
dc.subject | regulatory T lymphocyte | en |
dc.subject | Western blotting | en |
dc.subject | Adult | en |
dc.subject | Apoptosis | en |
dc.subject | Blotting, Western | en |
dc.subject | Carnitine O-Palmitoyltransferase | en |
dc.subject | CD4-Positive T-Lymphocytes | en |
dc.subject | Cells, Cultured | en |
dc.subject | eIF-2 Kinase | en |
dc.subject | Fatty Acids | en |
dc.subject | Female | en |
dc.subject | Forkhead Transcription Factors | en |
dc.subject | Humans | en |
dc.subject | Indoleamine-Pyrrole 2,3,-Dioxygenase | en |
dc.subject | Lymphocyte Activation | en |
dc.subject | Lymphocyte Culture Test, Mixed | en |
dc.subject | Male | en |
dc.subject | Nuclear Receptor Subfamily 1, Group F, Member 3 | en |
dc.subject | Oxidation-Reduction | en |
dc.subject | Phosphorylation | en |
dc.subject | Protein-Serine-Threonine Kinases | en |
dc.subject | T-Lymphocytes, Regulatory | en |
dc.subject | Tryptophan | en |
dc.subject | Spandidos Publications | en |
dc.title | Indoleamine 2,3-dioxygenase, by degrading L-tryptophan, enhances carnitine palmitoyltransferase i activity and fatty acid oxidation, and exerts fatty acid-dependent effects in human alloreactive CD4+ T-cells | en |
dc.type | journalArticle | en |