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Tryptophan catabolism

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https://www.readbyqxmd.com/read/29437277/identification-of-native-and-post-translationally-modified-hla-b-57-01-restricted-hiv-envelope-derived-epitopes-using-immunoproteomics
#1
Sri H Ramarathinam, Stephanie Gras, Sheilajen Alcantara, Amanda W S Yeung, Nicole A Mifsud, Secondo Sonza, Patricia T Illing, Elias N Glaros, Robert J Center, Shane Thomas, Stephen J Kent, Nicola Ternette, Damian F J Purcell, Jamie Rossjohn, Anthony W Purcell
The recognition of pathogen-derived peptides by T lymphocytes is the cornerstone of adaptive immunity, whereby intracellular antigens are degraded in the cytosol and short peptides assemble with class I human leukocyte antigen (HLA) molecules in the endoplasmic reticulum (ER). These peptide-HLA complexes egress to the cell surface and are scrutinized by cytotoxic CD8+ T-cells leading to the eradication of the infected cell. Here we identify naturally presented HLA-B*57:01 bound peptides derived from the envelope protein of the human immunodeficiency virus (HIVenv)...
February 13, 2018: Proteomics
https://www.readbyqxmd.com/read/29415228/plasma-tryptophan-kynurenine-metabolites-are-altered-in-hiv-infection-and-associated-with-progression-of-carotid-artery-atherosclerosis
#2
Qibin Qi, Simin Hua, Clary B Clish, Justin M Scott, David B Hanna, Tao Wang, Sabina A Haberlen, Sanjiv J Shah, Marshall J Glesby, Jason M Lazar, Robert D Burk, Howard N Hodis, Alan L Landay, Wendy S Post, Kathryn Anastos, Robert C Kaplan
Background: It is unknown whether disrupted tryptophan catabolism is associated with cardiovascular disease (CVD) in HIV-infected individuals. Methods: Plasma tryptophan and kynurenic acid were measured among 737 women and men (520 HIV+, 217 HIV-) from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. Repeated B-mode carotid artery ultrasound imaging was obtained among these participants in 2004-2013. We examined associations of baseline plasma tryptophan, kynurenic acid, and kynurenic acid-to-tryptophan (KYNA/TRP) ratio, a measure of tryptophan catabolism, with risk of carotid artery plaque...
February 3, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29413890/indoleamine-2-3-dioxygenase-and-its-therapeutic-inhibition-in-cancer
#3
George C Prendergast, William J Malachowski, Arpita Mondal, Peggy Scherle, Alexander J Muller
The tryptophan catabolic enzyme indoleamine 2,3-dioxygenase-1 (IDO1) has attracted enormous attention in driving cancer immunosuppression, neovascularization, and metastasis. IDO1 suppresses local CD8+ T effector cells and natural killer cells and induces CD4+ T regulatory cells (iTreg) and myeloid-derived suppressor cells (MDSC). The structurally distinct enzyme tryptophan dioxygenase (TDO) also has been implicated recently in immune escape and metastatic progression. Lastly, emerging evidence suggests that the IDO1-related enzyme IDO2 may support IDO1-mediated iTreg and contribute to B-cell inflammed states in certain cancers...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29413421/inflammatory-reprogramming-with-ido1-inhibitors-turning-immunologically-unresponsive-cold-tumors-hot
#4
REVIEW
George C Prendergast, Arpita Mondal, Souvik Dey, Lisa D Laury-Kleintop, Alexander J Muller
We discuss how small-molecule inhibitors of the tryptophan (Trp) catabolic enzyme indoleamine 2,3-dioxygenase (IDO) represent a vanguard of new immunometabolic adjuvants to safely enhance the efficacy of cancer immunotherapy, radiotherapy, or 'immunogenic' chemotherapy by leveraging responses to tumor neoantigens. IDO inhibitors re-program inflammatory processes to help clear tumors by blunting tumor neovascularization and restoring immunosurveillance. Studies of regulatory and effector pathways illuminate IDO as an inflammatory modifier...
January 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29406815/dysregulation-of-tryptophan-catabolism-in-metabolic-syndrome
#5
Neila Hiraishi Mallmann, Emerson Silva Lima, Pritesh Lalwani
OBJECTIVE: Obesity and metabolic syndrome are preventable complex-multifactorial disorders that severely increase risk of cardiovascular disease (CVD). Indoleamine 2,3-dioxygenase (IDO) enzyme converts tryptophan (TRP) to kynurenine (KYN); besides, KYN/TRP ratio has been shown to predict major coronary events and all-cause mortality in patients with coronary artery disease. However, their role in metabolic syndrome is not understood. METHODS: In a cross-sectional study (n = 161, mean population age in years = 32 ± 7...
February 6, 2018: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/29393500/indoleamine-2-3-dioxygenase-regulation-of-immune-response-review
#6
Hao Wu, Jianping Gong, Yong Liu
Indoleamine 2, 3-dioxygenase (IDO) catalyzes the initial and rate‑limiting step in the degradation pathway of the essential amino acid tryptophan and is expressed by professional antigen presenting cells (APCs), epithelial cells, vascular endothelium and tumor cells. IDO‑mediated catabolic products, which are additionally termed 'kynurenines', exerts important immunosuppressive functions primarily via regulating T effector cell anergy and inducing the proliferation of T regulatory cells. This endogenous tolerogenic pathway has a critical effect on mediating the magnitude of immune responses under various stress conditions, including tumor, infection and transplantation...
February 1, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29335800/enrichment-and-characterization-of-a-bacterial-mixture-capable-of-utilizing-c-mannosyl-tryptophan-as-a-carbon-source
#7
Tanim J Hossain, Shino Manabe, Yukishige Ito, Toshiya Iida, Saori Kosono, Kenji Ueda, Akira Hosomi, Daishi Inoue, Tadashi Suzuki
C-Mannosylation, a protein-modification found in various eukaryotes, involves the attachment of a single mannose molecule to selected tryptophan residues of proteins. Since C-mannosyl tryptophan (CMW) was detected in human urine, it is generally thought that CMW is not catabolized inside our body and instead is excreted via the urine. This paper reports enrichment of a bacterial consortium from soil that degrades CMW. The bacteria grew in minimal medium supplemented with CMW as the carbon source. Interestingly, even after successive clonal picks of individual colonies, several species were still present in each colony as revealed by 16S rRNA gene sequence analysis, indicating that a single species may not be responsible for this activity...
January 15, 2018: Glycoconjugate Journal
https://www.readbyqxmd.com/read/29327354/a-validated-liquid-chromatography-high-resolution-tandem-mass-spectrometry-method-for-the-simultaneous-quantitation-of-tryptophan-kynurenine-kynurenic-acid-and-quinolinic-acid-in-human-plasma
#8
Kathrin Arnhard, Florian Pitterl, Barbara Sperner-Unterweger, Dietmar Fuchs, Therese Koal, Herbert Oberacher
Tryptophan (TRP) catabolism via the kynurenine pathway is considered to represent a major link between inflammation and various diseases, including neurodegenerative disorders, depression, schizophrenia, multiple sclerosis, cardiovascular disease, and cancer. The kynurenine pathway and levels of TRP and its metabolites kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QUIN) are well regulated under physiological conditions but may be altered as part of the activated immune response. A simple, sensitive and specific liquid chromatography-time of flight mass spectrometry method was developed for determining levels of the four compounds in human plasma samples...
January 12, 2018: Electrophoresis
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
#9
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
#10
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/29190885/the-ido-inhibitor-1-methyl-tryptophan-activates-the-aryl-hydrocarbon-receptor-response-in-mesenchymal-stromal-cells
#11
Holly C Lewis, Raghavan Chinnadurai, Steven E Bosinger, Jacques Galipeau
The catabolism of tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is a key step in tolerance effected by a variety of cell types, including mesenchymal stromal cells (MSCs). Trp catabolism generates molecules known as kynurenines, whose tolerance mechanisms involve activation of the Aryl Hydrocarbon Receptor (AHR). A synthetic analog of Trp, 1-methyl tryptophan (1MT), is a selective inhibitor of IDO enzymatic activity being utilized in cancer immunotherapy trials. We hypothesized 1MT might activate AHR independently of its effects on IDO...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163470/indoleamine-2-3-dioxygenase-and-tolerance-where-are-we-now
#12
REVIEW
Andrew L Mellor, Henrique Lemos, Lei Huang
Cells expressing IDO suppress innate and adaptive immunity to promote tolerance by catabolizing the amino acid tryptophan (Trp) and other indole compounds. Interferon type I (IFN-I) and type II (IFN-II) produced at sites of inflammation or by activated immune cells are potent IDO inducers because mammalian IDO genes contain IFN response elements. Elevated IDO expression by dendritic cells (DCs) is of particular significance because IDO activity converts mature DCs into tolerogenic APCs that suppress effector T cells (Teff) and promote regulatory T cells (Tregs), thereby promoting tolerance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29154462/the-role-of-indoleamine-2-3-dioxygenase-in-normal-and-pathological-pregnancies
#13
REVIEW
Rui-Qi Chang, Da-Jin Li, Ming-Qing Li
The survival of allogeneic fetus during pregnancy contradicts the laws of immune responses. Behind this paradoxical phenomenon, the mechanism is quite complex. Indoleamine-2,3-dioxygenase (IDO) is the first and rate-limiting enzyme of tryptophan catabolism. Emerging evidence shows that IDO is expressed at the maternal-fetal interface, including trophoblast cells, decidual stroma cells, decidual immune cells (eg, natural killer cells, T cells, and macrophages), and vascular endothelial cells of decidua and chorion...
November 20, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29141444/associations-among-obesity-inflammation-and-tryptophan-catabolism-in-pregnancy
#14
Maureen Groer, Dietmar Fuchs, Allyson Duffy, Adetola Louis-Jacques, Amy D'Agata, Teodor T Postolache
OBJECTIVE: To evaluate relationships among obesity in pregnancy and plasma levels of tryptophan (TRP) and kynurenine (KYN), inflammatory markers, and depressed mood. METHODS: Pregnant women ( N = 374) were enrolled, and data were collected at a mean gestation of 20 weeks in this cross-sectional study. Plasma was analyzed for TRP, KYN, neopterin, and nitrite levels. Women completed demographic and mood scales. RESULTS: There was a statistically significant inverse correlation between body mass index (BMI) and TRP and positive correlations between BMI and KYN and the kynurenine/tryptophan (KYN/TRP) ratio...
January 1, 2017: Biological Research for Nursing
https://www.readbyqxmd.com/read/29118261/erratum-for-the-research-article-dysbiosis-of-the-gut-microbiota-is-associated-with-hiv-disease-progression-and-tryptophan-catabolism-by-i-vujkovic-cvijin-r-m-dunham-s-iwai-m-c-maher-r-g-albright-m-j-broadhurst-r-d-hernandez-m-m-lederman-y-huang-m-somsouk-s
#15
https://www.readbyqxmd.com/read/29113177/potential-role-of-indoleamine-2-3-dioxygenase-in-primary-biliary-cirrhosis
#16
Kashif Asghar, John Brain, Jeremy M Palmer, Stephen Douglass, Fatmah M A Naemi, Graeme O'Boyle, John Kirby, Simi Ali
Indoleamine 2,3-dioxygenase (IDO)-induced immunosuppression can be clinically beneficial for autoimmune diseases. Primary biliary cirrhosis (PBC) is characterized by autoimmune lesions of intrahepatic bile duct epithelial cells that may lead to irreversible cirrhosis or hepatocellular carcinoma. The present study assessed the expression and function of IDO in a cell culture model and in PBC patients. IDO expression was monitored in a human immortalized but non-malignant biliary epithelial cell (iBEC) line. Increased expression of IDO1/2 was observed in the iBECs following stimulation with interferon-γ (IFN-γ)...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29111717/discovery-of-a-novel-and-selective-indoleamine-2-3-dioxygenase-ido-1-inhibitor-3-5-fluoro-1h-indol-3-yl-pyrrolidine-2-5-dione-eos200271-pf-06840003-and-its-characterization-as-a-potential-clinical-candidate
#17
Stefano Crosignani, Patrick Bingham, Pauline Bottemanne, Hélène Cannelle, Sandra Cauwenberghs, Marie Cordonnier, Deepak Dalvie, Frederik Deroose, Jun Li Feng, Bruno Gomes, Samantha Greasley, Stephen E Kaiser, Manfred Kraus, Michel Négrerie, Karen Maegley, Nichol Miller, Brion W Murray, Manfred Schneider, James Soloweij, Albert E Stewart, Joseph Tumang, Vince R Torti, Benoit Van Den Eynde, Martin Wythes
Tumors use tryptophan-catabolizing enzymes such as indoleamine 2,3-dioxygenase (IDO-1) to induce an immunosuppressive environment. IDO-1 is induced in response to inflammatory stimuli and promotes immune tolerance through effector T-cell anergy and enhanced Treg function. As such, IDO-1 is a nexus for the induction of a key immunosuppressive mechanism and represents an important immunotherapeutic target in oncology. Starting from HTS hit 5, IDO-1 inhibitor 6 (EOS200271/PF-06840003) has been developed. The structure-activity relationship around 6 is described and rationalized using the X-ray crystal structure of 6 bound to human IDO-1, which shows that 6, differently from most of the IDO-1 inhibitors described so far, does not bind to the heme iron atom and has a novel binding mode...
December 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29099929/transcriptome-assessment-of-erythema-migrans-skin-lesions-in-patients-with-early-lyme-disease-reveals-predominant-interferon-signaling
#18
Adriana Marques, Ira Schwartz, Gary P Wormser, Yanmei Wang, Ronald L Hornung, Cumhur Y Demirkale, Peter J Munson, Siu-Ping Turk, Carla Williams, Chyi-Chia Richard Lee, Jun Yang, Mary M Petzke
Background: The most common clinical manifestation of early Lyme disease is the erythema migrans (EM) skin lesion that develops at the tick bite site typically between 7 and 14 days following infection with Borreliella burgdorferi. The host-pathogen interactions that occur in the skin may have a critical role in determining outcome of infection. Methods: Gene arrays were utilized to characterize the global transcriptional alterations in skin biopsy samples of EM lesions from untreated adult patients with Lyme disease in comparison to controls...
November 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29080891/prenatal-dynamics-of-kynurenine-pathway-metabolism-in-mice-focus-on-kynurenic-acid
#19
Nick Goeden, Francesca M Notarangelo, Ana Pocivavsek, Sarah Beggiato, Alexandre Bonnin, Robert Schwarcz
The kynurenine pathway (KP), the major catabolic route of tryptophan in mammals, contains several neuroactive metabolites, including kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK). KP metabolism, and especially the fate of KYNA, during pregnancy is poorly understood, yet it may play a significant role in the development of psychiatric disorders later in life. The present study was designed to investigate the prenatal features of KP metabolism in vivo, with special focus on KYNA. To this end, pregnant CD-1 mice were treated systemically with kynurenine (100 mg/kg), KYNA (10 mg/kg), or saline on embryonic day 18...
October 28, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/29080383/clinical-significance-of-tryptophan-catabolism-in-hodgkin-lymphoma
#20
Ayako Masaki, Takashi Ishida, Yasuhiro Maeda, Asahi Ito, Susumu Suzuki, Tomoko Narita, Shiori Kinoshita, Hisashi Takino, Takashi Yoshida, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Hiroshi Inagaki, Ryuzo Ueda, Ilseung Choi, Youko Suehiro, Shinsuke Iida
Indoleamine 2,3-dioxygenase 1 (IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway. The purpose of the present study was to determine the clinical significance of Trp catabolism in newly-diagnosed Hodgkin Lymphoma (HL) patients. We quantified serum Trp and Kyn in 52 HL patients, and analyzed their associations with different clinical parameters including serum soluble CD30 (sCD30) concentration. IDO expression was evaluated in the patients' affected lymph nodes. The enrolled patients comprised 22 males and 30 females (age range 15-81, median 45 years), with a 5-year overall survival (OS) of 88...
October 28, 2017: Cancer Science
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