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Indoleamine

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https://www.readbyqxmd.com/read/29331741/extracellular-acidification-induces-ros-and-mptp-mediated-death-in-hek293-cells
#1
José Teixeira, Farhan Basit, Herman G Swarts, Marleen Forkink, Paulo J Oliveira, Peter H G M Willems, Werner J H Koopman
The extracellular pH (pHe) is a key determinant of the cellular (micro)environment and needs to be maintained within strict boundaries to allow normal cell function. Here we used HEK293 cells to study the effects of pHe acidification (24h), induced by mitochondrial inhibitors (rotenone, antimycin A) and/or extracellular HCl addition. Lowering pHe from 7.2 to 5.8 reduced cell viability by 70% and was paralleled by a decrease in cytosolic pH (pHc), hyperpolarization of the mitochondrial membrane potential (Δψ), increased levels of hydroethidine-oxidizing ROS and stimulation of protein carbonylation...
December 30, 2017: Redox Biology
https://www.readbyqxmd.com/read/29322062/increased-indoleamine-2-3-dioxygenase-activity-is-associated-with-poor-clinical-outcome-in-adults-hospitalized-with-influenza-in-the-insight-flu003plus-study
#2
Sarah L Pett, Ken M Kunisaki, Deborah Wentworth, Timothy J Griffin, Ioannis Kalomenidis, Raquel Nahra, Rocio Montejano Sanchez, Shane W Hodgson, Kiat Ruxrungtham, Dominic Dwyer, Richard T Davey, Chris H Wendt
Background: Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. Methods: We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up...
January 2018: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/29305519/antigen-specific-antitumor-responses-induced-by-ox40-agonist-are-enhanced-by-ido-inhibitor-indoximod
#3
Zuzana Berrong, Mikayel Mkrtichyan, Shamim Ahmad, Mason Webb, Eslam Mohamed, Grigori Okoev, Adelaida Matevosyan, Rajeev Shrimali, Rasha Abu Eid, Scott Hammond, John E Janik, Samir N Khleif
Although an immune response to tumors may be generated using vaccines, so far, this approach has only shown minimal clinical success. This is attributed to the tendency of cancer to escape immune surveillance via multiple immune suppressive mechanisms. Successful cancer immunotherapy requires targeting these inhibitory mechanisms along with enhancement of antigen-specific immune responses to promote sustained tumor-specific immunity. Here we evaluated the effect of indoximod, an inhibitor of the immunosuppressive indoleamine-(2,3)-dioxygenase (IDO) pathway, on antitumor efficacy of anti-OX40 agonist in the context of vaccine in the IDO- TC-1 tumor model...
January 5, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29302770/modulating-tumor-immunology-by-inhibiting-indoleamine-2-3-dioxygenase-ido-recent-developments-and-first-clinical-experiences
#4
Diwakar Davar, Nathan Bahary
Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) catalyze the first rate-limiting step in the oxidative metabolism of compounds containing indole rings, including the transformation of the essential amino acid L-tryptophan to N-formyl-L-kynurenine. Through direct and indirect means, IDO exerts both tolerogenic and pro-inflammatory effects and has a profound immunoregulatory role in the tumor microenvironment. Although the role of IDO in mediating peripheral acquired immunologic tolerance has been known for some time, its role in tumorigenesis and the subversion of anti-tumor immunity have only recently been appreciated...
January 4, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29302217/caffeic-acid-phenethyl-ester-protects-against-photothrombotic-cortical-ischemic-injury-in-mice
#5
Sun Ae Hwang, Chi Dae Kim, Won Suk Lee
In this study, we aimed to investigate the neuroprotective effects of caffeic acid phenethyl ester (CAPE), an active component of propolis purified from honeybee hives, on photothrombotic cortical ischemic injury in mice. Permanent focal ischemia was achieved in the medial frontal and somatosensory cortices of anesthetized male C57BL/6 mice by irradiation of the skull with cold light laser in combination with systemic administration of rose bengal. The animals were treated with CAPE (0.5-5 mg/kg, i.p.) twice 1 and 6 h after ischemic insult...
January 2018: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/29301550/role-of-the-indoleamine-2-3-dioxygenase-kynurenine-pathway-of-tryptophan-metabolism-in-behavioral-alterations-in-a-hepatic-encephalopathy-rat-model
#6
Xi Jiang, Lexing Xu, Lin Tang, Fuhe Liu, Ziwei Chen, Jiajia Zhang, Lei Chen, Cong Pang, Xuefeng Yu
BACKGROUND: This study aims to explore the role of indoleamine-2,3-dioxygenase (IDO)/kynurenine (KYN) pathway of tryptophan (TRY) metabolism in behavioral alterations observed in hepatic encephalopathy (HE) rats. METHODS: Expression levels of proinflammatory cytokines were tested by QT-PCR and ELISA, levels of IDOs were tested by QT-PCR and Western blot, and levels of 5-hydroxytryptamine (5-HT), KYN, TRY, 3-hydroxykynurenine (3-HK), and kynurenic acid (KA) in different brain regions were estimated using HPLC...
January 4, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29296775/th17-immune-microenvironment-in-epstein-barr-virus-negative-hodgkin-lymphoma-implications-for-immunotherapy
#7
Amy S Duffield, Maria Libera Ascierto, Robert A Anders, Janis M Taube, Alan K Meeker, Shuming Chen, Tracee L McMiller, Neil A Phillips, Haiying Xu, Aleksandra Ogurtsova, Alan E Berger, Drew M Pardoll, Suzanne L Topalian, Richard F Ambinder
Classical Hodgkin lymphoma (CHL) is a neoplasm characterized by robust inflammatory infiltrates and heightened expression of the immunosuppressive PD-1/PD-L1 pathway. Although anti-PD-1 therapy can be effective in >60% of patients with refractory CHL, improved treatment options are needed for CHLs which are resistant to anti-PD-1 or relapse after this form of immunotherapy. A deeper understanding of immunologic factors in the CHL microenvironment might support the design of more effective treatment combinations based on anti-PD-1...
July 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296736/novel-gm-csf-signals-via-ifn-%C3%AE-r-irf-1-and-akt-mtor-license-monocytes-for-suppressor-function
#8
Eliana Ribechini, James A Hutchinson, Sabine Hergovits, Marion Heuer, Jörg Lucas, Ulrike Schleicher, Ana-Laura Jordán Garrote, Sarah J Potter, Paloma Riquelme, Heike Brackmann, Nora Müller, Hartmann Raifer, Ingolf Berberich, Magdalena Huber, Andreas Beilhack, Michael Lohoff, Christian Bogdan, Matthias Eyrich, Heike M Hermanns, Edward K Geissler, Manfred B Lutz
Granulocyte-macrophage colony-stimulating factor (GM-CSF) controls proliferation and survival of myeloid cells including monocytes. Here, we describe a time-dependent licensing process driven by GM-CSF in murine Ly6Chigh and human CD14+ monocytes that disables their inflammatory functions and promotes their conversion into suppressor cells. This 2-step licensing of monocytes requires activation of the AKT/mTOR/mTORC1 signaling cascade by GM-CSF followed by signaling through the interferon-γ receptor (IFN-γR)/interferon regulatory factor-1 (IRF-1) pathway...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296206/indoleamine-2-3-dioxygenase-and-interleukin-6-associated-with-tumor-response-to-neoadjuvant-chemotherapy-in-breast-cancer
#9
Fangxuan Li, Lijuan Wei, Shixia Li, Juntian Liu
Purpose: Indoleamine-2,3-dioxygenase (IDO) and Interleukin-6 (IL-6) contribute to poor therapeutic effects, tumor relapse and aggressive tumor growth. IDO and IL-6 incorporate a positive feedback signal loop to maintain IDO and IL-6 constitutive expression and facilitate tumor progression. Results: IDO expression was associated with IL-6 expression and plasma IL-6 level (P<0.05). Concentrating on clinicopathological features prior neoadjuvant chemotherapy, both IDO expression and plasma IL-6 level were associated with clinical T stage and N stage (P<0...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29288671/prolonged-skin-grafts-survival-time-by-ifn-%C3%AE-in-allogeneic-skin-transplantation-model-during-acute-rejection-through-ifn-%C3%AE-stat3-ido-pathway-in-epidermal-layer
#10
Yijie Zhang, Yunchuan Wang, Gaofeng Wu, Wei Zhang, Xujie Wang, Weixia Cai, Julei Zhang, Shichao Han, Yan Li, Xiaozhi Bai, Jihong Shi, Linlin Su, Dahai Hu
Allogeneic skin transplantation is the life-saving therapy for multiple diseases, including extensive burn, large-scale trauma and certain post-surgical complications. However, acute rejection impedes clinical application of allogeneic skin transplantation. Although a lot of novel immunosuppressant drugs have been developed, there is still great need for ideal therapy with less complication and more therapeutic effects. Here, we found interferon gamma (IFN-γ) as an immunomodulatory cytokine prolonged the survival time of allografts from (8...
December 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29288638/a-single-amino-acid-residue-regulates-the-substrate-affinity-and-specificity-of-indoleamine-2-3-dioxygenase
#11
Hajime J Yuasa, Mayumi Sugiura, Terue Harumoto
Indoleamine 2,3-dioxygenase (IDO) is a heme-containing enzyme that catalyses the oxidative cleavage of L-Trp. The ciliate Blepharisma stoltei has four IDO genes (IDO-I, -II, -III and -IV), which seem to have evolved via two sequential gene duplication events. Each IDO enzyme has a distinct enzymatic property, where IDO-III ha-s a high affinity for L-Trp, whereas the affinity of the other three isoforms for L-Trp is low. IDO-I also exhibits a significant catalytic activity with another indole compound: 5-hydroxy-L-tryptophan (5-HTP)...
December 27, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29278387/indoleamine-2-3-dioxygenase-ido-enzyme-links-innate-immunity-and-altered-t-cell-differentiation-in-non-st-segment-elevation-acute-coronary-syndrome
#12
Chiara Zara, Anna Severino, Davide Flego, Aureliano Ruggio, Daniela Pedicino, Ada Francesca Giglio, Francesco Trotta, Claudia Lucci, Domenico D'Amario, Ramona Vinci, Eugenia Pisano, Giulio La Rosa, Luigi Marzio Biasucci, Filippo Crea, Giovanna Liuzzo
Atherosclerosis is a chronic inflammatory disease characterized by a complex interplay between innate and adaptive immunity. Dendritic cells (DCs) play a key role in T-cell activation and regulation by promoting a tolerogenic environment through the expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO), an intracellular enzyme involved in tryptophan catabolism. IDO expression and activity was analyzed in monocytes derived DCs (MDDCs) from non-ST segment elevation myocardial infarction (NSTEMI) patients, stable angina (SA) patients and healthy controls (HC) by real-time quantitative polymerase chain reaction (RT-qPCR) before and after in vitro maturation with lipopolysaccharide (LPS)...
December 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29275469/tryptophan-catabolism-and-cancer-immunotherapy-targeting-ido-mediated-immune-suppression
#13
Adaobi Amobi, Feng Qian, Amit A Lugade, Kunle Odunsi
Over the last decade, tryptophan catabolism has been firmly established as a powerful mechanism of innate and adaptive immune tolerance. The catabolism of tryptophan is a central pathway maintaining homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses. This is driven by the key and rate-limiting enzymes indoleamine-2,3-dioxygenase 1 (IDO1) and tryptophan-2,3-dioxygenase 2 (TDO), resulting in local depletion of tryptophan, while tryptophan catabolites accumulate, including kynurenine and its derivatives, depending on the presence of downstream enzymes in the kynurenine pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29275467/chemo-immunotherapy-role-of-indoleamine-2-3-dioxygenase-in-defining-immunogenic-versus-tolerogenic-cell-death-in-the-tumor-microenvironment
#14
Theodore S Johnson, Tracy Mcgaha, David H Munn
In certain settings, chemotherapy can trigger an immunogenic form of tumor cell death. More often, however, tumor cell death after chemotherapy is not immunogenic, and may be actively tolerizing. However, even in these settings the dying tumor cells may be much more immunogenic than previously recognized, if key suppressive immune checkpoints such as indoleamine 2,3-dioxygenase (IDO) can be blocked. This is an important question, because a robust immune response to dying tumor cells could potentially augment the efficacy of conventional chemotherapy, or enhance the strength and duration of response to other immunologic therapies...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29259700/neuroprotective-effects-of-human-umbilical-cord-derived-mesenchymal-stem-cells-on-periventricular-leukomalacia-like-brain-injury-in-neonatal-rats
#15
Chikako Morioka, Motohiro Komaki, Atsuko Taki, Izumi Honda, Naoki Yokoyama, Kengo Iwasaki, Sachiko Iseki, Tomohiro Morio, Ikuo Morita
Background: Periventricular leukomalacia (PVL) is a type of multifactorial brain injury that causes cerebral palsy in premature infants. To date, effective therapies for PVL have not been available. In this study, we examined whether mesenchymal stem cells (MSCs) possess neuroprotective property in a lipopolysaccharide (LPS)-induced neonatal rat PVL-like brain injury. Methods: Human umbilical cord-derived MSCs (UCMSCs) were used in this study. Four-day-old rats were intraperitoneally injected with LPS (15 mg/kg) to cause the PVL-like brain injury and were treated immediately after the LPS-injection with UCMSCs, conditioned medium prepared from MSCs (UCMSC-CM) or interferon-gamma (IFN-γ)-pretreated MSC (IFN-γ-UCMSC-CM)...
2017: Inflammation and Regeneration
https://www.readbyqxmd.com/read/29247038/discovery-of-ido1-inhibitors-from-bench-to-bedside
#16
REVIEW
George C Prendergast, William P Malachowski, James B DuHadaway, Alexander J Muller
Small-molecule inhibitors of indoleamine 2,3-dioxygenase-1 (IDO1) are emerging at the vanguard of experimental agents in oncology. Here, pioneers of this new drug class provide a bench-to-bedside review on preclinical validation of IDO1 as a cancer therapeutic target and on the discovery and development of a set of mechanistically distinct compounds, indoximod, epacadostat, and navoximod, that were first to be evaluated as IDO inhibitors in clinical trials. As immunometabolic adjuvants to widen therapeutic windows, IDO inhibitors may leverage not only immuno-oncology modalities but also chemotherapy and radiotherapy as standards of care in the oncology clinic...
December 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/29241670/glia-and-tissue-specific-changes-in-the-kynurenine-pathway-after-treatment-of-mice-with-lipopolysaccharide-and-dexamethasone
#17
Carlos R Dostal, Nicolaus S Gamsby, Marcus A Lawson, Robert H McCusker
Behavioral symptoms associated with mood disorders have been intimately linked with immunological and psychological stress. Induction of immune and stress pathways is accompanied by increased tryptophan entry into the Kynurenine (Kyn) Pathway as governed by the rate-limiting enzymes indoleamine/tryptophan 2,3-dioxygenases (DO's: Ido1, Ido2, Tdo2). Indeed, elevated DO expression is associated with inflammation- and stress-related depression symptoms. Here we examined central (brain, astrocyte and microglia) and peripheral (lung, liver and spleen) DO expression in mice treated intraperitoneally with lipopolysaccharide (LPS) and dexamethasone (DEX) to model the response of the Kyn Pathway to inflammation and glucocorticoids...
December 11, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29240291/novel-4-amino-1-2-3-triazole-inhibitors-of-indoleamine-2-3-dioxygenase-form-a-long-lived-complex-with-the-enzyme-and-display-exquisite-cellular-potency
#18
Julie Alexandre, Michael Swan, Mike Latchem, Dean Boyall, John Pollard, Stuart Hughes, James Westcott
Indoleamine-2,3 dioxygenase (IDO) has emerged as a central regulator of immune responses in both normal and disease biology. Due to its established role in promoting tumour immune escape, IDO has become an attractive target for cancer treatment. We have identified a novel series of highly cell potent IDO inhibitors based on a 4-amino-1,2,3-triazole core. Comprehensive kinetic, biochemical and structural studies demonstrate that compounds from this series have a non-competitive kinetic mechanism-of-action with respect to the tryptophan substrate...
December 14, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29238069/kynurenic-acid-an-ido-metabolite-controls-tsg-6-mediated-immunosuppression-of-human-mesenchymal-stem-cells
#19
Guan Wang, Kai Cao, Keli Liu, Yueqing Xue, Arthur I Roberts, Fengying Li, Yanyan Han, Arnold B Rabson, Ying Wang, Yufang Shi
Mesenchymal stem cells (MSCs) have been demonstrated to be anti-inflammatory against various immune disorders through several factors, including indoleamine 2,3-dioxygenase (IDO) and TNF-stimulated gene 6 (TSG-6). However, little is known about the necessity for both of these key immunosuppressive factors. Here we employed the mouse lipopolysaccharide (LPS)-induced acute lung injury (ALI) model, and found that IDO is necessary to achieve the effect of human umbilical cord-derived MSC (hUC-MSC)-based treatment on ALI...
December 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29226383/bifidobacterium-alleviated-experimentally-induced-colitis-by-upregulating-in-doleamine-2-3-dioxygenase-expression
#20
Li Zhao, Yangzhen Suolang, Dandan Zhou, Yu Tang, Yan Zhang
The goal of this study was explore the role of indoleamine 2, 3-dioxygenase (IDO) in the therapeutic effect of probiotics on inflammatory bowel disease (IBD). Trinitro-benzene sulfonic acid (TNBS) was used to induce colitis in mice, and 1-methyltryptophan (1-MT) was used to block the expression of IDO. Clinical manifes-tations, macroscopic and microscopic colonic alterations were assessed using the dis-ease activity index (DAI), Wallace-Keenan, and Curtner scoring systems, respectively. The expression of colonic IDO was detected by western blot...
December 11, 2017: Microbiology and Immunology
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