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Indoleamine 2,3-dioxygenase

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https://www.readbyqxmd.com/read/28107600/the-predictive-and-prognostic-role-of-serum-neopterin-and-tryptophan-breakdown-in-prostate-cancer
#1
Renate Pichler, Josef Fritz, Isabel Heidegger, Eberhard Steiner, Zoran Culig, Helmut Klocker, Dietmar Fuchs
The Interferon-gamma induced enzymes indoleamine 2,3-dioxygenase and GTP-cylohydrolase are key players in tumor immune escape mechanisms. We quantified serum levels of neopterin and tryptophan breakdown (tryptophan, kynurenine and kynurenine-to-tryptophan ratio) in addition to prostate-specific antigen (PSA) in newly diagnosed prostate cancer (PCa) patients (n=100) before radical prostatectomy (RP) as well as at time of biochemical recurrence (BCR) after RP (n=50) in comparison to healthy men (n=49). Effects of biomarkers on the risk of PCa diagnosis on transrectal biopsy, worse histopathological characteristics of the RP specimens and cancer-specific survival (CSS) after BCR were investigated...
January 20, 2017: Cancer Science
https://www.readbyqxmd.com/read/28098246/tryptophan-metabolite-activation-of-the-aryl-hydrocarbon-receptor-regulates-il-10-receptor-expression-on-intestinal-epithelia
#2
J M Lanis, E E Alexeev, V F Curtis, D A Kitzenberg, D J Kao, K D Battista, M E Gerich, L E Glover, D J Kominsky, S P Colgan
IL-10 is a potent anti-inflammatory cytokine that inhibits the production of proinflammatory mediators. Signaling by IL-10 occurs through the IL-10 receptor (IL-10R), which is expressed in numerous cell types, including intestinal epithelial cells (IECs), where it is associated with development and maintenance of barrier function. Guided by an unbiased metabolomics screen, we identified tryptophan (Trp) metabolism as a major modifying pathway in interferon-γ (IFNγ)-dominant murine colitis. In parallel, we demonstrated that IFNγ induction of indoleamine 2,3-dioxygenase 1, an enzyme that catalyzes the conversion of Trp to kynurenine (Kyn), induces IL-10R1 expression...
January 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28078987/role-of-proinflammatory-cytokines-in-dopaminergic-system-disturbances-implications-for-anhedonic-features-of-mdd
#3
Zihang Pan, Joshua D Rosenblat, Walter Swardfager, Roger S McIntyre
Anhedonia, characterized by a loss of interest and/or pleasure in previously enjoyable activities, is an important diagnostic criterion of Major Depressive Disorder (MDD). Converging evidence implicates a behaviouralcausal relationship between proinflammatory cytokines and disturbances that characterize anhedonia in the context of MDD. Additionally, anhedonia has been implicated in disturbances of key central dopaminergic modulatory pathways. Emerging research into the roles of tetrahydrobiopterin, a cytokine-targeted co-enzyme in the synthesis of dopamine, and kynurenine, a product of inflammation-sensitive breakdown of tryptophan via indoleamine 2, 3-dioxygenase, have shed new light into the role of inflammation in mediating anhedonic behaviours...
January 11, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28077574/platelet-activating-factor-mediates-endotoxin-tolerance-by-regulating-indoleamine-2-3-dioxygenase-dependent-expression-of-the-suppressor-of-cytokine-signaling-3
#4
Kyung Tae Noh, In Duk Jung, Gil Sun Cha, Myung-Kwan Han, Yeong-Min Park
Indoleamine 2, 3-dioxygenase (IDO) mediates immune tolerance, and suppressor of cytokine signaling 3 (SOCS3) negatively regulates the JAK/STAT signal transduction pathway. We previously determined plateletactivating factor (PAF) protects mice against lipopolysaccharide (LPS)-induced endotoxic shock, but its detailed mechanism of action was unknown. We performed survival experiments in IDO+/+ and IDO-/- mice using an LPSinduced endotoxemia model and rated organ injury (neutrophil infiltration, and liver function)...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28077028/ferulic-acid-suppresses-expression-of-tryptophan-metabolic-key-enzyme-indoleamine-2-3-dioxygenase-via-nf%C3%AE%C2%BAb-and-p38-mapk-in-lipopolysaccharide-stimulated-microglial-cells
#5
Manami Koshiguchi, Hitoshi Komazaki, Shizuka Hirai, Yukari Egashira
Ferulic acid (FA) is a phenol compound found in plants that has anti-inflammatory properties. Indoleamine 2, 3-dioxygenase (IDO) is a tryptophan catabolic enzyme induced in immune cells, including glial cells, during inflammation. Enhanced IDO expression leads to reduced tryptophan levels and increased levels of toxic metabolites, including quinolinic acid. Therefore, inhibition of IDO expression may be effective in suppressing progression of neurodegenerative diseases. In this study, we examined the effect of FA in microglial cells on IDO expression levels and related inflammatory signal molecules...
January 12, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28076309/activation-of-the-tryptophan-serotonin-pathway-is-associated-with-severity-and-predicts-outcomes-in-pneumonia-results-of-a-long-term-cohort-study
#6
Marc A Meier, Manuel Ottiger, Alaadin Vögeli, Christian Steuer, Luca Bernasconi, Robert Thomann, Mirjam Christ-Crain, Christoph Henzen, Claus Hoess, Werner Zimmerli, Andreas Huber, Beat Mueller, Philipp Schuetz
BACKGROUND: As part of the immune defense during infection, an increase in enzyme activity of indoleamine 2,3-dioxygenase (IDO) leads to a breakdown of tryptophan to kynurenine. In previous animal studies, therapeutic antagonism of IDO resulted in reduced sepsis mortality. We investigated the prognostic ability of tryptophan, serotonin, kynurenine and IDO (represented by the ratio of kynurenine/tryptophan) to predict adverse clinical outcomes in patients with community-acquired pneumonia (CAP)...
January 11, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28065794/adjuvant-quercetin-therapy-for-combined-treatment-of-epilepsy-and-comorbid-depression
#7
Tanveer Singh, Taranjot Kaur, Rajesh Kumar Goel
Epilepsy is one of the major neurological disorders frequently associated with psychiatric disorders such as depression. The predisposition of tryptophan metabolism towards kynurenine pathway has been reported as one of the plausible reasons for association of depression in epilepsy. Hence, this study was envisaged to evaluate the dose dependent inhibition of indoleamine 2,3-dioxygenase (IDO) enzyme employing quercetin (screened employing in vitro method) with levetiracetam for combined management of epilepsy and comorbid depression...
January 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28057727/indoleamine-2-3-dioxygenase-activity-is-associated-with-regulatory-t-cell-response-in-acute-puumala-hantavirus-infection
#8
Tuisku-Tuulia Koivula, Anni Tuulasvaara, Iivo Hetemäki, Mikko Hurme, Satu Mäkelä, Jukka Mustonen, Antti Vaheri, T Petteri Arstila
High indoleamine 2,3-dioxygenase (IDO) activity is associated with clinically severe acute infection caused by Puumala hantavirus. The immunoregulatory effects of IDO can be mediated either through metabolic control of effector T cells, caused by depletion of the essential amino acid tryptophan, or intercellular signaling and activation of regulatory T cell responses. Here we have studied 24 patients with acute PUUV infection to distinguish between these possibilities. Maximum IDO activity showed a significant positive correlation with FOXP3 expression levels in regulatory T cells, a quantitative surrogate marker for suppressive capability...
January 5, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28053021/first-in-human-phase-1-study-of-the-oral-inhibitor-of-indoleamine-2-3-dioxygenase-1-epacadostat-incb024360-in-patients-with-advanced-solid-malignancies
#9
Gregory L Beatty, Peter J O'Dwyer, Jason Clark, Jack G Shi, Kevin J Bowman, Peggy Scherle, Robert C Newton, Richard Schaub, Janet Maleski, Lance Leopold, Thomas F Gajewski
PURPOSE: Indoleamine 2,3-dioxygenase-1 (IDO1) catalyzes the degradation of tryptophan to N-formyl-kynurenine. Overexpressed in many solid malignancies, IDO1 can promote tumor escape from host immunosurveillance. This first-in-human phase 1 study investigated the maximum tolerated dose, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of epacadostat (INCB024360), a potent and selective inhibitor of IDO1. PATIENTS AND METHODS: Fifty-two patients with advanced solid malignancies were treated with epacadostat (50 mg once daily or 50, 100, 300, 400, 500, 600, or 700 mg twice daily [BID]) in a dose-escalation 3 + 3 design and evaluated in 28-day cycles...
January 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28042544/indoleamine-2-3-dioxygenase-is-dispensable-for-the-immunomodulatory-function-of-stem-cells-from-human-exfoliated-deciduous-teeth
#10
Razieh Alipour, Masoumeh Masoumi Karimi, Batool Hashemi-Beni, Minoo Adib, Nasrin Sereshki, Farzaneh Sadeghi
OBJECTIVE: In this study, we sought to better understand the immunoregulatory function of stem cells derived from human exfoliated deciduous teeth (SHED). We studied the role of the interferon gamma (IFN-γ)-indoleamine 2,3-dioxygenase (IDO)-axis in immunoregulation of SHED compared to bone marrow derived mesenchymal stem cells (BMMSCs) under the same conditions. MATERIALS AND METHODS: In this cross-sectional study, recently isolated human T cells were stimulated either by mitogen or inactivated allogeneic peripheral blood mononuclear cells (PBMCs)...
2017: Cell Journal
https://www.readbyqxmd.com/read/28038393/managing-epilepsy-associated-depression-serotonin-enhancers-or-serotonin-producers
#11
REVIEW
Tanveer Singh, Rajesh Kumar Goel
Depression is one of the major psychiatric comorbidities having a major impact on the quality of life in people with epilepsy (PWE). Selective serotonin reuptake inhibitors (SSRIs) are considered as safest therapy for the treatment of depression in PWE. Although administration of SSRIs increases the synaptic serotonin levels, it decreases the overall serotonin synthesis in the brain. Long-term therapy with SSRIs has been reported to decrease serotonin synthesis, which may be the possible reason for lessening of their antidepressant effect over time as well as elevated seizure outcomes observed in PWE...
December 27, 2016: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28035211/induction-of-indoleamine-2-3-dioxygenase-by-pre-treatment-with-poly-i-c-may-enhance-the-efficacy-of-msc-treatment-in-dss-induced-colitis
#12
Da-Bin Ryu, Ji-Young Lim, Sung-Eun Lee, Gyeongsin Park, Chang-Ki Min
Mesenchymal stem cells (MSCs) have been used experimentally for treating inflammatory disorders, partly owing to their immunosuppressive properties. The goal of the study was to determine whether TLR ligands can enhance the therapeutic efficacy of bone marrow-derived MSCs for the treatment of inflammatory bowel disease. Mice (C57BL6) were administered with 4% dextran sulfate sodium (DSS) in drinking water for 7 days and injected with MSCs on days 1 and 3 following DSS ingestion. Our results demonstrated that among various TLR ligands, MSCs treated with polyinosinic-polycytidylic acid [poly(I:C)], which is a TLR3 ligand, more profoundly induced IDO, which is a therapeutically relevant immunosuppressive factor, without any observable phenotype change in vitro...
December 2016: Immune Network
https://www.readbyqxmd.com/read/28024468/-expression-and-activity-regulation-of-indoleamine-2-3-dioxygenase-in-acute-myeloid-leukemia-cells
#13
Jing Liao, Yu-Pin Li, Jian-Ming Huang, Ge Li
OBJECTIVE: To investigate the expression and activity regulation of indoleamine 2,3-dioxygenase(IDO) in acute myeloid leukemia cells. METHODS: Expression of IDO and TLR9 in HL-60 and K562 cells cocultured with or without IFN-γ,Tα1,IFN-γ+Tα1 and chloroquine were determined by reverse transcription-polymerase chain reaction(RT-PCR). Then, the IDO activity in HL-60 and K562 cells cocultured with or without IFN-γ,Tα1,IFN-γ+ Tα1 was assayed by coomassie brilliant blue staining and modified colorimetric method...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28011425/discovery-and-evaluation-of-inhibitors-to-the-immunosuppressive-enzyme-indoleamine-2-3-dioxygenase-1-ido1-probing-the-active-site-inhibitor-interactions
#14
Petr Tomek, Brian D Palmer, Jack U Flanagan, Chuanwen Sun, Emma L Raven, Lai-Ming Ching
High expression of the immunosuppressive enzyme, indoleamine 2,3-dioxygenase 1 (IDO1) for a broad range of malignancies is associated with poor patient prognosis, and the enzyme is a validated target for cancer intervention. To identify novel IDO1 inhibitors suitable for drug development, 1597 compounds in the National Cancer Institute Diversity Set III library were tested for inhibitory activity against recombinant human IDO1. We retrieved 35 hits that inhibited IDO1 activity >50% at 20 μM. Five structural filters and the PubChem Bioassay database were used to guide the selection of five inhibitors with IC50 between 3 and 12 μM for subsequent experimental evaluation...
December 13, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28004656/co-delivery-of-indoleamine-2-3-dioxygenase-prevents-loss-of-expression-of-an-antigenic-transgene-in-dystrophic-mouse-muscles
#15
D Sharma, R Al-Khalidi, S Edgar, Q An, Y Wang, C Young, D Nowis, D C Gorecki
A significant problem affecting gene therapy approaches aiming at achieving long-term transgene expression is the immune response against the protein product of the therapeutic gene, which can reduce or eliminate the therapeutic effect. The problem is further exacerbated when therapy involves targeting an immunogenic tissue and/or one with a pre-existing inflammatory phenotype, such as dystrophic muscles. In this proof-of-principle study, we co-expressed a model antigen, bacterial β-galactosidase, with an immunosuppressive factor, indoleamine 2,3-dioxygenase 1 (IDO1), in muscles of the mdx mouse model of Duchenne muscular dystrophy...
December 22, 2016: Gene Therapy
https://www.readbyqxmd.com/read/28003141/identification-and-optimization-of-a-novel-series-of-indoleamine-2-3-dioxygenase-inhibitors
#16
Jay A Markwalder, Steven P Seitz, Yuval Blat, Lisa Elkin, John T Hunt, Jonathan G Pabalan, Maria N Jure-Kunkel, Gregory D Vite, Kelly Covello
The discovery of a series of structurally-novel biaryl urea IDO inhibitors is described. Optimization of a micromolar hit through iterative cycles of synthesis and screening in an assay measuring IDO-mediated intracellular conversion of tryptophan to kynurenine led to potent inhibitors with favorable selectivity and metabolic stability profiles.
December 7, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28000524/modulation-of-cancer-specific-immune-responses-by-amino-acid-degrading-enzymes
#17
Elina Timosenko, Andreas V Hadjinicolaou, Vincenzo Cerundolo
To evade immune destruction, tumors exploit a wide range of immune escape mechanisms, including the induction of an immunosuppressive tumor microenvironment. This is mediated, in part, by amino acid degrading enzymes indoleamine 2,3-dioxygenase, tryptophan 2,3-dioxygenase, arginase 1 and arginase 2, which have emerged as key players in the regulation of tumor-induced immune tolerance. Here we describe how the expression of tryptophan- and arginine-degrading enzymes by tumor and tumor-infiltrating cells can hamper cancer-specific immune responses, and discuss how this knowledge is being exploited to develop new strategies for cancer immunotherapy...
January 2017: Immunotherapy
https://www.readbyqxmd.com/read/27995404/circulating-zonulin-correlates-with-density-of-enteroviruses-and-tolerogenic-dendritic-cells-in-the-small-bowel-mucosa-of-celiac-disease-patients
#18
Tamara Vorobjova, Helerin Raikkerus, Lumme Kadaja, Ija Talja, Oivi Uibo, Kaire Heilman, Raivo Uibo
BACKGROUND: Impaired intestinal integrity, including increased permeability of the small bowel mucosa, has been shown in patients with celiac disease (CD) as well as with type 1 diabetes (T1D). Zonulin (ZO, pre-haptoglobin), a tight junction regulator, plays a particular role in the regulation of intestinal barrier function and in the pathogenesis of the above-mentioned diseases. AIM: To investigate whether enteroviruses (EVs) and immunoregulatory cells are associated with intestinal permeability in patients with CD alone and with coexistent T1D...
December 19, 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/27994758/fused-heterocyclic-compounds-as-potent-indoleamine-2-3-dioxygenase-1-inhibitors
#19
Subhankar Panda, Ashalata Roy, Suman Jyoti Deka, Vishal Trivedi, Debasis Manna
Uncontrolled metabolism of l-tryptophan (l-Trp) in the immune system has been recognized as a critical cellular process in immune tolerance. Indoleamine 2,3-dioxygenase 1 (IDO1) enzyme plays an important role in the metabolism of a local l-Trp through the kynurenine pathway in the immune systems. In this regard, IDO1 has emerged as a therapeutic target for the treatment of diseases that are associated with immune suppression like chronic infections, cancer, and others. In this study, we synthesized a series of pyridopyrimidine, pyrazolopyranopyrimidine, and dipyrazolopyran derivatives...
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27994058/signal-transducer-and-activator-of-transcription-1-plays-a-pivotal-role-in-ret-ptc3-oncogene-induced-expression-of-indoleamine-2-3-dioxygenase-1
#20
Sonia Moretti, Elisa Menicali, Nicole Nucci, Pasquale Voce, Renato Colella, Rosa Marina Melillo, Federica Liotti, Silvia Morelli, Francesca Fallarino, Antonio Macchiarulo, Massimo Santoro, Nicola Avenia, Efisio Puxeddu
Indoleamine 2,3-dioxygenase 1 (IDO1) is a single chain oxidoreductase that catalyzes tryptophan degradation to kynurenine. In cancer, it exerts an immunosuppressive function as part of an acquired mechanism of immune-escape. Recently, we demonstrated that IDO1 expression is significantly higher in all thyroid cancer histotypes compared to normal thyroid and that its expression levels correlate with T regulatory (Treg) lymphocyte densities in the tumor microenvironment. BRAFV600E- and RET/PTC3-expressing PcCL3 cells were used as cellular models for the evaluation of IDO1 expression in thyroid carcinoma cells and for the study of involved signal transduction pathways...
December 19, 2016: Journal of Biological Chemistry
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