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Indoleamine 2,3-dioxygenase

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https://www.readbyqxmd.com/read/28434116/activation-of-the-serotonin-pathway-is-associated-with-poor-outcome-in-copd-exacerbation-results-of-a-long-term-cohort-study
#1
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/INTRODUCTION: Indoleamine 2,3-dioxygenase (IDO) metabolizes tryptophan to kynurenine. An increase of its activity is associated with severity in patients with pneumonia. In chronic obstructive pulmonary disease (COPD) patients, an elevation of serotonin has been reported. Experimental models showed that cigarette smoke inhibits monoamine oxidase (MAO) leading to higher levels of serotonin. We investigated the prognostic ability of tryptophan, serotonin, kynurenine, IDO, and tryptophan hydroxylase (TPH) to predict short- and long-term outcomes in patients with a COPD exacerbation...
April 22, 2017: Lung
https://www.readbyqxmd.com/read/28432455/dual-activation-of-toll-like-receptors-7-and-9-impairs-the-efficacy-of-antitumor-vaccines-in-murine-models-of-metastatic-breast-cancer
#2
Mariela A Moreno Ayala, María Florencia Gottardo, María Soledad Gori, Alejandro Javier Nicola Candia, Carla Caruso, Andrea De Laurentiis, Mercedes Imsen, Slobodanka Klein, Elisa Bal de Kier Joffé, Gabriela Salamone, Maria G Castro, Adriana Seilicovich, Marianela Candolfi
PURPOSE: Since combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models. METHODS: DCs were generated from mouse bone marrow or peripheral blood from healthy human donors and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9 agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated in BALB/c mice bearing metastatic mammary adenocarcinomas...
April 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28428708/indoleamine-2-3-dioxygenase-as-a-potential-prognostic-marker-and-immunotherapeutic-target-for-hepatocellular-carcinoma
#3
REVIEW
Kashif Asghar, Asim Farooq, Bilal Zulfiqar, Muhammad Usman Rashid
Tumor cells induce an immunosuppressive microenvironment which leads towards tumor immune escape. Understanding the intricacy of immunomodulation by tumor cells is essential for immunotherapy. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme which mediates tumor immune escape in various cancers including hepatocellular carcinoma (HCC). IDO up-regulation in HCC may lead to recruitment of regulatory T-cells into tumor microenvironment and therefore inhibit local immune responses and promote metastasis...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28424423/the-antidepressant-like-effect-of-trans-astaxanthin-involves-the-serotonergic-system
#4
Xi Jiang, Keqi Zhu, Quanyi Xu, Guokang Wang, Jiajia Zhang, Rongrong Cao, Jiang Ye, Xuefeng Yu
The antidepressant-like effect of trans-astaxanthin, a compound present rich in algae, was evaluated through behavioral and neurochemical methods. Results showed that trans-astaxanthin treatment significantly decreased the immobility time in force swim test and tail suspension test, but did not influence locomotor activity. Trans-astaxanthin treatment did not effectively antagonize hypothermia and ptosis induced by reserpine. However, pre-treatment with para-chlorophenylalanine abolished the anti-immobility effect of trans-astaxanthin in force swim and tail suspension test...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414589/progesterone-decreases-in-vitro-indoleamine-2-3-dioxygenase-expression-in-dendritic-and-cd4-cells-from-maternal-fetal-interface-of-rats
#5
Pedro Kastein Faria da Cunha Bianchi, Rafael Magdanelo Leandro, Aline Nayara Poscai, Tulio Yoshinaga, Patrícia Orlandini Gonçalez, José Roberto Kfoury Junior
PROBLEM: Several mechanisms contribute to the tolerogenic state observed during pregnancy, such as the activity of the enzyme indoleamine 2, 3-dioxygenase (IDO). This initializes the catabolism of tryptophan, inducing T cells to apoptosis due to its deprivation and by the action of its catabolites in the placental microenvironment. Progesterone plays an important part on immunological tolerance mechanisms during pregnancy; however, there is no evidence it is related to IDO activity. Thus, this study aimed to investigate progesterone influence on the maternal-fetal interface of pregnant Wistar rats, by identifying IDO positive cells by immunophenotyping and flow cytometry under exogenous progesterone supplementation...
April 17, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28412361/structural-insights-into-the-binding-mechanism-of-ido1-with-hydroxylamidine-based-inhibitor-incb14943
#6
You Wu, Tingting Xu, Jinsong Liu, Ke Ding, Jinxin Xu
IDO1 (indoleamine 2, 3-dioxygenase 1), a well characterized immunosuppressive enzyme, has attracted growing attention as a potential target for cancer immunotherapy. Hydroxylamidine compounds INCB024360 and INCB14943 (INCB024360 analogue) are highly effective IDO1 inhibitors. INCB024360 is undergoing clinical trials for treatment of various types of human cancer. Here, we determined the co-crystal structure of IDO1 and INCB14943, and elucidate the detailed binding mode. INCB14943 binds to heme iron in IDO1 protein through the oxime nitrogen...
April 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28406643/polyketides-and-anthranilic-acid-possessing-6-deoxy-%C3%AE-l-talopyranose-from-a-streptomyces-species
#7
Sangkeun Son, Sung-Kyun Ko, Mina Jang, Jae Kyoung Lee, Min Cheol Kwon, Dong Hyo Kang, In-Ja Ryoo, Jung-Sook Lee, Young-Soo Hong, Bo Yeon Kim, Jae-Hyuk Jang, Jong Seog Ahn
A bioassay-guided investigation in conjunction with chemical screening led to the isolation of three new glycosides, ulleungoside (1), 2-methylaminobenzoyl 6-deoxy-α-l-talopyranoside (2), and naphthomycinoside (3), along with three known secondary metabolites (5-7) from Streptomyces sp. KCB13F030. Their structures were elucidated by detailed NMR and MS spectroscopic analyses. Absolute configurational analysis of the sugar units based on the magnitudes of the coupling constants, NOESY correlations, chemical derivatization, and optical rotation measurements revealed that compounds 1-3 and 5 incorporate the rare deoxyhexose 6-deoxy-α-l-talopyranose...
April 13, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28405495/biological-and-clinical-significance-of-tryptophan-catabolizing-enzymes-in-cutaneous-t-cell-lymphomas
#8
Pilvi Maliniemi, Kirsi Laukkanen, Liisa Väkevä, Katja Dettmer, Tuomas Lipsanen, Leila Jeskanen, Alban Bessede, Peter J Oefner, Marshall E Kadin, Annamari Ranki
Indoleamine 2,3-deoxygenase 1 (IDO1) induces immune tolerance in the tumor microenvironment (TME) and is recognized as a potential therapeutic target. We studied the expression of both IDO1 and the related tryptophan 2,3-dioxygenase (TDO) in several different subtypes of cutaneous T-cell lymphoma (CTCL), and evaluated the kynurenine (KYN) pathway in the local TME and in patient sera. Specimens from the total of 90 CTCL patients, including mycosis fungoides (MF, n = 37), lymphomatoid papulosis (LyP, n = 36), primary cutaneous anaplastic large cell lymphoma (pcALCL, n = 4), subcutaneous panniculitis-like T-cell lymphoma (SPTCL n = 13), and 10 patients with inflammatory lichen ruber planus (LRP), were analyzed by immunohistochemistry (IHC), immunofluorescence (IF), quantitative PCR, and/or liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28403684/mangiferin-prevents-corticosterone-induced-behavioural-deficits-via-alleviation-of-oxido-nitrosative-stress-and-down-regulation-of-indoleamine-2-3-dioxygenase-ido-activity
#9
Gao-Quan Luo, Ling Liu, Qu-Wen Gao, Xiao-Na Wu, Wei Xiang, Wen-Ting Deng
BACKGROUND: In recent years, a substantial amount of experimental studies have demonstrated that exogenous administration of corticosterone causes anxiety and depressive-like behaviour in rodents which involves hypothalamic-pituitary-adrenal axis dysregulation. Our present study aimed to explore the neuroprotective potential of mangiferin against corticosterone-induced anxiety and depressive-like behaviour. METHODS: Corticosterone (40 mg/kg; subcutaneously) was administered once daily in swiss albino mice for 21 days...
April 12, 2017: Neurological Research
https://www.readbyqxmd.com/read/28401366/resistance-to-immunotherapy-clouds-in-a-bright-sky
#10
REVIEW
Gérard Milano
Two major challenges persist for an optimal management of immunotherapy: i) identifying those patients who will benefit from this type of therapy, and ii) determining the biological, cellular and molecular mechanisms that trigger disease progression while on therapy. There is a consensual view in favor of standardizing practices currently used to measure programmed death ligand 1 (PD-L1) expression that relates to innate resistance. The tumor mutation landscape has been widely explored as a potential predictor of treatment efficacy...
April 12, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28377795/crosstalk-between-tryptophan-metabolism-and-cardiovascular-disease-mechanisms-and-therapeutic-implications
#11
REVIEW
Gang Liu, Shuai Chen, Jin Zhong, Kunling Teng, Yulong Yin
The cardiovascular diseases (CVD) associated with the highest rates of morbidity are coronary heart disease and stroke, and the primary etiological factor leading to these conditions is atherosclerosis. This long-lasting inflammatory disease, characterized by how it affects the artery wall, results from maladaptive immune responses linked to the vessel wall. Tryptophan (Trp) is oxidized in a constitutive manner by tryptophan 2,3-dioxygenase in liver cells, and for alternative cell types, it is catalyzed in the presence of a differently inducible indoleamine 2,3-dioxygenase (IDO1) in the context of a specific pathophysiological environment...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28376268/ahr-mediates-an-anti-inflammatory-feed-back-mechanism-in-human-langerhans-cells-involving-fc%C3%AE%C2%B5ri-and-ido
#12
Susanne Koch, Tim J Stroisch, Julia Vorac, Nadine Herrmann, Nicole Leib, Sylvia Schnautz, Helene Kirins, Irmgard Förster, Heike Weighardt, Thomas Bieber
BACKGROUND: Aryl hydrocarbon receptor (AhR), an important regulator of immune responses, is activated by UVB irradiation in the skin. Langerhans cells (LC) in the epidermis of atopic dermatitis (AD) patients carry the high affinity receptor for IgE, FcεRI, and are crucially involved in the pathogenesis of AD by inducing inflammatory responses and regulating tolerogenic processes. OBJECTIVES: We investigated AhR and AhR repressor (AhRR) expression and functional consequences of AhR activation in human ex vivo skin cells and in in vitro generated LC...
April 4, 2017: Allergy
https://www.readbyqxmd.com/read/28372497/astrocyte-mediated-inflammation-in-cortical-spreading-depression
#13
Amir Ghaemi, Leila Alizadeh, Shahnaz Babaei, Maryam Jafarian, Maryam Khaleghi Ghadiri, Sven G Meuth, Stjepana Kovac, Ali Gorji
Background Cortical spreading depression (CSD) related diseases such as migraine, cerebrovascular diseases, and epilepsy have been associated with reactive astrocytosis, yet the mechanisms of these tissue changes remain unclear. CSD-induced inflammatory response has been proposed to play a role in some neurological disorders and thus may also contribute to reactive astrocytosis. Methods Using ex vivo brain slices and in vitro astrocytic cultures, we aimed to characterize CSD related changes in astrocytes and markers of inflammation by immunocyto- and immunohistochemistry...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28344890/suppression-of-indoleamine-2-3-dioxygenase-1-expression-by-promoter-hypermethylation-in-er-positive-breast-cancer
#14
Dyah L Dewi, Soumya R Mohapatra, Saioa Blanco Cabañes, Isabell Adam, Luis F Somarribas Patterson, Bianca Berdel, Masroor Kahloon, Loreen Thürmann, Stefanie Loth, Katharina Heilmann, Dieter Weichenhan, Oliver Mücke, Ines Heiland, Pauline Wimberger, Jan Dominik Kuhlmann, Karl-Heinz Kellner, Sarah Schott, Christoph Plass, Michael Platten, Clarissa Gerhäuser, Saskia Trump, Christiane A Opitz
Kynurenine formation by tryptophan-catabolic indoleamine-2,3-dioxygenase 1 (IDO1) plays a key role in tumor immune evasion and inhibition of IDO1 is efficacious in preclinical models of breast cancer. As the response of breast cancer to immune checkpoint inhibitors may be limited, a better understanding of the expression of additional targetable immunomodulatory pathways is of importance. We therefore investigated the regulation of IDO1 expression in different breast cancer subtypes. We identified estrogen receptor α (ER) as a negative regulator of IDO1 expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344860/il-32-induces-indoleamine-2-3-dioxygenase-cd1c-dendritic-cells-and-indoleamine-2-3-dioxygenase-cd163-macrophages-relevance-to-mycosis-fungoides-progression
#15
Hanako Ohmatsu, Daniel Humme, Juana Gonzalez, Nicholas Gulati, Markus Möbs, Wolfram Sterry, James G Krueger
Mycosis fungoides (MF) progresses from patch to tumor stage by expansion of malignant T-cells that fail to be controlled by protective immune mechanisms. In this study, we focused on IL-32, a cytokine, highly expressed in MF lesions. Depending on the other cytokines (IL-4, GM-CSF) present during in vitro culture of healthy volunteers' monocytes, IL-32 increased the maturation of CD11c(+) myeloid dendritic cells (mDC) and/or CD163(+) macrophages, but IL-32 alone showed a clear ability to promote dendritic cell (DC) differentiation from monocytes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28337956/acute-renal-graft-versus-host-disease-in-a-murine-model-of-allogeneic-bone-marrow-transplantation
#16
Peter M Schmid, Abdellatif Bouazzaoui, Karin Schmid, Christoph Birner, Christian Schach, Lars S Maier, Ernst Holler, Dierk H Endemann
Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and associated with poor prognosis. Generally kidneys are assumed to be no direct target of Graft-versus-Host Disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully MHC-mismatched model of BALB/c mice conditioned and transplanted according to two different intensity protocols...
March 23, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28337881/indoleamine-2-3-dioxygenase-and-regulatory-t-cells-in-intestinal-mucosa-in-children-with-inflammatory-bowel-disease
#17
K Sznurkowska, A Żawrocki, J Sznurkowski, E Iżycka-Świeszewska, P Landowski, A Szlagatys-Sidorkiewicz, K Plata-Nazar, B Kamińska
Impaired immune regulation has been suggested as an underlying mechanism of inflammatory bowel disease. Indoleamine 2,3-dioxygenase (IDO) and regulatory T cells expressing FOXP3 are crucial elements of immune regulation. Conversion of FOXP3- lymphocytes to Tregs is one of the functions of IDO. The aim of this study was to evaluate the number of cells expressing FOXP3 and IDO in the lamina propria of intestinal mucosa and to evaluate correlations between these parameters and disease activity. Sixty-six children newly diagnosed with inflammatory bowel disease (41 patients with ulcerative colitis and 25 patients with Crohn’s disease) were included in the study...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28336214/indoleamine-2-3-dioxygenase-1-ido1-inhibitors-activate-the-aryl-hydrocarbon-receptor
#18
Benjamin J Moyer, Itzel Y Rojas, Iain A Murray, Seokwon Lee, Haley F Hazlett, Gary H Perdew, Craig R Tomlinson
Indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in the immune system by regulating tryptophan levels and T cell differentiation. Several tumor types overexpress IDO1 to avoid immune surveillance making IDO1 of interest as a target for therapeutic intervention. As a result, several IDO1 inhibitors are currently being tested in clinical trials for cancer treatment as well as several other diseases. Many of the IDO1 inhibitors in clinical trials naturally bear structural similarities to the IDO1 substrate tryptophan, as such, they fulfill many of the structural and functional criteria as potential AHR ligands...
March 20, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28324751/the-rationale-of-indoleamine-2-3-dioxygenase-inhibition-for-cancer-therapy
#19
REVIEW
Lieve Brochez, Ines Chevolet, Vibeke Kruse
Indoleamine 2,3-dioxygenase (IDO, also referred to as IDO1) has been demonstrated to be a normal endogenous mechanism of acquired peripheral immune tolerance in vivo. In the field of oncology, IDO expression and/or activity has been observed in several cancer types and has usually been associated with negative prognostic factors and worse outcome measures. This manuscript reviews current available data on the role of IDO in cancer and the current results obtained with IDO inhibition, both in animal models and in phase 1 and 2 clinical trials in humans...
March 18, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28320838/early-immune-regulatory-changes-in-a-primary-controlled-human-plasmodium-vivax-infection-cd1c-mdc-maturation-arrest-induction-of-the-kynurenine-pathway-and-regulatory-t-cell-activation
#20
Tonia Woodberry, Jessica R Loughland, Gabriela Minigo, Julie G Burel, Fiona H Amante, Kim A Piera, Yvette McNeil, Tsin W Yeo, Michael F Good, Denise L Doolan, Christian R Engwerda, James S McCarthy, Nicholas M Anstey
Plasmodium vivax malaria remains a major public health problem. The requirements for acquisition of protective immunity to this species are not clear. Dendritic cells (DC) are essential for immune cell priming, but also perform immune-regulatory functions, along with regulatory T cells (Treg). An important function of DC involves activation of the kynurenine pathway via indoleamine 2,3-dioxygenase (IDO). Using a controlled human experimental infection study with blood-stage P. vivax, we characterised plasmacytoid DC (pDC) and myeloid DC (mDC) subset maturation, CD4(+)CD25(+)CD127(lo) Treg activation and IDO activity...
March 20, 2017: Infection and Immunity
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