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Indoleamine 2,3-dioxygenase

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https://www.readbyqxmd.com/read/28912017/indoleamine-2-3-dioxygenase-1-increased-in-human-gastric-pre-neoplasia-promotes-inflammation-and-metaplasia-in-mice-and-is-associated-with-type-ii-hypersensitivity-autoimmunity
#1
Mohamad El-Zaatari, Adam J Bass, Reanne Bowlby, Min Zhang, Li-Jyun Syu, Yitian Yang, Helmut Grasberger, Andrew Shreiner, Bei Tan, Shrinivas Bishu, Wai K Leung, Andrea Todisco, Nobuhiko Kamada, Marilia Cascalho, Andrzej A Dlugosz, John Y Kao
BACKGROUND & AIMS: Chronic gastrointestinal inflammation increases the risk of cancer by mechanisms that are not well understood. Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-binding enzyme that regulates the immune response via catabolization and regulation of tryptophan availability for immune cell uptake. IDO1 expression is increased during the transition from chronic inflammation to gastric metaplasia. We investigated whether IDO1 contributes to the inflammatory response that mediates loss of parietal cells leading to metaplasia...
September 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28911850/activation-of-indoleamine-2-3-dioxygenase-pathway-by-olanzapine-augments-antidepressant-effects-of-venlafaxine-in-mice
#2
Jaya Thomas, Razia Khanam, Divya Vohora
Recent clinical studies report antipsychotics as a better option to augment the action of antidepressants in treatment resistant cases. However, the proper mechanisms underlying the antidepressant effect of antipsychotics is still not clear. Indolamine 2, 3 dioxygenase (IDO) pathway is considered to be an important pathway in pro-inflammatory cytokine associated stress-induced depression. The present study investigated the antidepressant effect of venlafaxine, olanzapine and their combinations in chronic forced-swim stress-induced depression in mice...
August 31, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28901958/pilot-study-of-the-tart-cherry-juice-for-the-treatment-of-insomnia-and-investigation-of-mechanisms
#3
Jack N Losso, John W Finley, Namrata Karki, Ann G Liu, Alfredo Prudente, Russell Tipton, Ying Yu, Frank L Greenway
BACKGROUND: Insomnia is common in the elderly and is associated with chronic disease, but use of hypnotics increases the incidence of falls. Montmorency tart cherry juice has improved insomnia by self-report questionnaire. STUDY QUESTION: Is insomnia confirmed by polysomnography and is tryptophan availability a potential mechanism for treating insomnia? STUDY DESIGN: A placebo-controlled balanced crossover study with subjects older than 50 years and insomnia were randomized to placebo (2 weeks) or cherry juice (2 weeks) (240 mL 2 times/d) separated by a 2-week washout...
March 27, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28901194/acute-renal-graft-versus-host-disease-in-a-murine-model-of-allogeneic-bone-marrow-transplantation
#4
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 is associated with a poor prognosis. Generally, the kidneys are assumed to not be no direct targets 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 major histocompatibility complex (MHC)-mismatched model of BALB/c mice conditioned and transplanted according to 2 different intensity protocols...
August 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28899580/the-interplay-between-cytokines-and-the-kynurenine-pathway-in-inflammation-and-atherosclerosis
#5
Roland Baumgartner, Maria J Forteza, Daniel F J Ketelhuth
The kynurenine pathway (KP) is the major metabolic route of tryptophan (Trp) metabolism. Indoleamine 2,3-dioxygenase (IDO1), the enzyme responsible for the first and rate-limiting step in the pathway, as well as other enzymes in the pathway, have been shown to be highly regulated by cytokines. Hence, the KP has been implicated in several pathologic conditions, including infectious diseases, psychiatric disorders, malignancies, and autoimmune and chronic inflammatory diseases. Additionally, recent studies have linked the KP with atherosclerosis, suggesting that Trp metabolism could play an essential role in the maintenance of immune homeostasis in the vascular wall...
September 9, 2017: Cytokine
https://www.readbyqxmd.com/read/28895862/immunomodulatory-effects-of-soluble-factors-secreted-by-feline-adipose-tissue-derived-mesenchymal-stem-cells
#6
Hyung-Kyu Chae, Woo-Jin Song, Jin-Ok Ahn, Qiang Li, Bo-Yeon Lee, Kyeong Kweon, Sang-Chul Park, Hwa-Young Youn
Mesenchymal stem cells (MSCs) have immunomodulatory functions and differentiation capacity, and their clinical use is increasing in veterinary species. Although MSCs have been applied in the treatment in various inflammatory diseases, mechanistic research on feline MSCs is lacking. Accordingly, in this study, we aimed to investigate the immunomodulatory mechanisms of MSCs isolated from feline adipose tissue (fATMSCs). fATMSCs from healthy cats were cultured in an appropriate manner and cocultured with transwell-separated allogeneic feline peripheral blood mononuclear cells (fPBMCs) and RAW264...
September 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28894451/inflammatory-conditions-dictate-the-effect-of-mesenchymal-stem-or-stromal-cells-on-b-cell-function
#7
Franka Luk, Laura Carreras-Planella, Sander S Korevaar, Samantha F H de Witte, Francesc E Borràs, Michiel G H Betjes, Carla C Baan, Martin J Hoogduijn, Marcella Franquesa
The immunomodulatory capacity of mesenchymal stem or stromal cells (MSC) makes them a promising tool for treatment of immune disease and organ transplantation. The effects of MSC on B cells are characterized by an abrogation of plasmablast formation and induction of regulatory B cells (Bregs). It is, however, unknown how MSC interact with B cells under inflammatory conditions. In this study, adipose tissue-derived MSC were pretreated with 50 ng/ml IFN-γ for 96 h (MSC-IFN-γ) to simulate inflammatory conditions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28886587/distinct-pattern-of-immune-tolerance-in-dendritic-cells-treated-with-lipopolysaccharide-or-lipoteichoic-acid
#8
Hyo Shin Yoon, Girak Kim, Young Jun Ju, In Su Cheon, Sun Woong Hong, Dong Wook Kim, Byung-Chul Park, Seung Hyun Han, Cheol-Heui Yun
Cytokine induction is often critical for the host defense during acute immune responses while, if not tightly regulated, it may cause an immunological pathology coincident with tissue damage. Despite the fact that gram-positive bacterial infection has become increasingly prevalent, immune modulation induced by lipoteichoic acid (LTA), the major cell wall component of gram-positive bacteria has not been studied thoroughly at the cellular level. In the current study, tolerance induction in mouse bone marrow-derived dendritic cells (BMDCs) treated with single or repeated stimulation of Staphylococcus aureus LTA was compared with those of Escherichia coli lipopolysaccharide (LPS)...
September 5, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28877670/indoleamine-2-3-dioxygenase-ido-increases-during-renal-fibrogenesis-and-its-inhibition-potentiates-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition
#9
Luiz Henrique Gomes Matheus, Gislene Mendes Simão, Taíssa Altieri Amaral, Rodrigo Barbosa Oliveira Brito, Camila Soares Malta, Yves Silva Teles Matos, Alexandre Chagas Santana, Gabriela Gomes Cardoso Rodrigues, Maria Clara Albejante, Erna Elisabeth Bach, Maria Aparecida Dalboni, Cleber Pinto Camacho, Humberto Dellê
BACKGROUND: Indoleamine 2, 3-dioxygenase (IDO) is an immunomodulatory molecule that has been implicated in several biological processes. Although IDO has been linked with some renal diseases, its role in renal fibrosis is still unclear. Because IDO may be modulated by TGF-β1, a potent fibrogenic molecule, we hypothesized that IDO could be involved in renal fibrosis, especially acting in the TGF-β1-induced tubular epithelial-mesenchymal transition (EMT). We analyzed the IDO expression and activity in a model of renal fibrogenesis, and the effect of the IDO inhibitor 1-methyl-tryptophan (MT) on TGF-β1-induced EMT using tubular cell culture...
September 6, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28871595/role-of-immune-microenvironment-in-gastrointestinal-stromal-tumors
#10
Andrew M Blakely, Andres Matoso, Pallavi A Patil, Ross Taliano, Jason T Machan, Thomas J Miner, Kara A Lombardo, Murray B Resnick, Li-Juan Wang
INTRODUCTION: The immune microenvironment is a prognostic factor for various malignancies. The significance of key players of this immune microenvironment including tumor-infiltrating lymphocytes and expression of programmed death-ligand 1 (PD-L1), indoleamine-2,3-dioxygenase (IDO), and tryptophanyl-tRNA synthetase (WARS) in gastrointestinal stromal tumors (GISTs) is largely unknown. METHODS: Tissue microarrays were constructed from pathology files, 1996-2016. Immunohistochemistry for PD-L1, IDO, WARS was correlated with tumor size, mitoses, and outcomes...
September 4, 2017: Histopathology
https://www.readbyqxmd.com/read/28864263/mechanism-of-chimeric-vaccine-stimulation-of-indoleamine-2-3-dioxygenase-biosynthesis-in-human-dendritic-cells-is-independent-of-tgf-%C3%AE-signaling
#11
Grace E Esebanmen, William H R Langridge
Cholera toxin B subunit fusion to autoantigens such as proinsulin (CTB-INS) down regulate dendritic cell (DC) activation and stimulate synthesis of DC immunosuppressive cytokines. Recent studies of CTB-INS induction of immune tolerance in human DCs indicate that increased biosynthesis of indoleamine 2,3-dioxygenase (IDO1) may play an important role in CTB-INS vaccine suppression of DC activation. Studies in murine models suggest a role for transforming growth factor beta (TGF-β) in the stimulation of IDO1 biosynthesis, for the induction of tolerance in DCs...
August 21, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28844802/recent-developments-in-small-molecule-therapies-for-renal-cell-carcinoma
#12
REVIEW
Minsoo Song
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and is known to be the 10th most common type of cancer in the world. Most of the currently available RCC drugs are tyrosine kinase inhibitors (TKIs). However, combination therapies of TKIs and immune checkpoint inhibitors such as programmed cell death protein 1 (PD-1) and programmed cell death protein 1 ligand 1 (PD-L1) inhibitors are the focus of most of the final stage clinical trials. Meanwhile, other small molecule therapies for RCC that target indoleamine-2,3-dioxygenase (IDO1), glutaminase, C-X-C chemokine receptor 4 (CXCR4), and transglutaminase 2 (TG2) are emerging as the next generation of therapeutics...
August 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28827067/increased-tryptophan-metabolism-is-associated-with-activity-of-inflammatory-bowel-diseases
#13
Susanna Nikolaus, Berenice Schulte, Natalie Al-Massad, Florian Thieme, Dominik M Schulte, Johannes Bethge, Ateequr Rehman, Florian Tran, Konrad Aden, Robert Häsler, Natalie Moll, Gregor Schütze, Markus J Schwarz, Georg H Waetzig, Philip Rosenstiel, Michael Krawczak, Silke Szymczak, Stefan Schreiber
BACKGROUND & AIMS: Administration of tryptophan, and some of its metabolites, reduces the severity of colitis in mice, whereas removing tryptophan from the diet increases susceptibility to colitis. Transfer of the intestinal microbiome can increase susceptibility of mice to colitis. We aimed to systematically evaluate serum levels of tryptophan and its metabolites in patients with inflammatory bowel diseases (IBD), and study their association with clinical and serologic features. METHODS: We studied 535 consecutive patients with IBD (211 with ulcerative colitis [UC], 234 with Crohn's disease [CD]; 236 male), enrolled in Germany from August 2013 through April 2014 and followed until July 2016...
August 18, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28805262/mesenchymal-stem-cells-attenuate-liver-fibrosis-by-suppressing-th17-cells
#14
Neda Milosavljevic, Marina Gazdic, Bojana Simovic Markovic, Aleksandar Arsenijevic, Jasmin Nurkovic, Zana Dolicanin, Nemanja Jovicic, Ilija Jeftic, Valentin Djonov, Nebojsa Arsenijevic, Miodrag L Lukic, Vladislav Volarevic
This study investigates molecular and cellular mechanisms involved in mesenchymal stem cell (MSCs)-mediated modulation of IL-17 signaling during liver fibrosis. Mice received CCl4 (1μL/g intraperitoneally) twice/week for 1 month. MSCs (1x10(6) ), or MSC-conditioned medium (MSC-CM) were intravenously injected 24h after CCl4 and on every 7(th) day. Liver fibrosis was determined by macroscopic examination, histological analysis, Sirius red staining and RT-PCR. Serum levels of cytokines, IDO and kynurenine were determined by ELISA...
August 14, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28801236/frailty-status-in-older-adults-is-related-to-alterations-in-indoleamine-2-3-dioxygenase-1-and-guanosine-triphosphate-cyclohydrolase-i%C3%A2-enzymatic-pathways
#15
Diego Marcos-Pérez, María Sánchez-Flores, Ana Maseda, Laura Lorenzo-López, José C Millán-Calenti, Barbara Strasser, Johanna M Gostner, Dietmar Fuchs, Eduardo Pásaro, Vanessa Valdiglesias, Blanca Laffon
BACKGROUND: Frailty is a multidimensional syndrome correlated to the loss of homeostasis and increased vulnerability to stressors, which is associated with increase in the risk of disability, comorbidity, hospitalization, and death in the elderly. It is based on the interplay of physiological, psychological, social, and environmental factors. OBJECTIVES: Because aging involves a detrimental immune response, this work aimed to assess the possible role of chronic low-grade immune stimulation on frailty status in the elderly...
August 8, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/28798777/mesenchymal-stem-cells-promote-metastasis-of-lung-cancer-cells-by-downregulating-systemic-antitumor-immune-response
#16
Marina Gazdic, Bojana Simovic Markovic, Nemanja Jovicic, Maja Misirkic-Marjanovic, Valentin Djonov, Vladimir Jakovljevic, Nebojsa Arsenijevic, Miodrag L Lukic, Vladislav Volarevic
Since majority of systemically administered mesenchymal stem cells (MSCs) become entrapped within the lungs, we used metastatic model of lung cancer, induced by intravenous injection of Lewis lung cancer 1 (LLC1) cells, to investigate the molecular mechanisms involved in MSC-mediated modulation of metastasis. MSCs significantly augmented lung cancer metastasis, attenuate concentrations of proinflammatory cytokines (TNF-α, IL-17), and increase levels of immunosuppressive IL-10, nitric oxide, and kynurenine in sera of LLC1-treated mice...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28791025/the-ido-ahr-axis-controls-th17-treg-immunity-in-a-pulmonary-model-of-fungal-infection
#17
Eliseu Frank de Araújo, Claudia Feriotti, Nayane Alves de Lima Galdino, Nycolas Willian Preite, Vera Lúcia Garcia Calich, Flávio Vieira Loures
In infectious diseases, the enzyme indoleamine 2,3 dioxygenase-1 (IDO1) that catalyzes the tryptophan (Trp) degradation along the kynurenines (Kyn) pathway has two main functions, the control of pathogen growth by reducing available Trp and immune regulation mediated by the Kyn-mediated expansion of regulatory T (Treg) cells via aryl hydrocarbon receptor (AhR). In pulmonary paracoccidioidomycosis (PCM) caused by the dimorphic fungus Paracoccidioides brasiliensis, IDO1 was shown to control the disease severity of both resistant and susceptible mice to the infection; however, only in resistant mice, IDO1 is induced by TGF-β signaling that confers a stable tolerogenic phenotype to dendritic cells (DCs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28790848/the-status-of-immunosuppression-in-patients-with-stage-iiib-or-iv-non-small-cell-lung-cancer-correlates-with-the-clinical-characteristics-and-response-to-chemotherapy
#18
Yuan Wang, Guo-Fang Hu, Zhe-Hai Wang
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step of tryptophan (Trp) degradation via the kynurenine (Kyn) pathway, which inhibits the proliferation of T cells and induces the apoptosis of T cells, leading to immune tolerance. Therefore, IDO has been considered as the most important mechanism for tumor cells to escape from immune response. Previous studies suggested that IDO might be involved in the progression of tumor and resistance to chemotherapy. Several preclinical and clinical studies have proven that IDO inhibitors can regulate IDO-mediated tumor immune escape and potentiate the effect of chemotherapy...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28771838/human-regulatory-macrophages-are-potent-in-suppression-of-the-xenoimmune-response-via-indoleamine-2-3-dioxygenase-involved-mechanism-s
#19
Fei Guo, Min Hu, Dandan Huang, Yuanfei Zhao, Benjamin Heng, Gilles Guillemin, Chai K Lim, Wayne J Hawthorne, Shounan Yi
BACKGROUND: For xenotransplantation to truly succeed, we must develop immunomodulatory strategies to suppress the xenoimmune response but by minimizing immunosuppression over the long term. Regulatory macrophages (Mreg) have been shown to suppress polyclonal T-cell proliferation in vitro and prolong allograft survival in vivo. However, the question of whether they are capable of suppressing xenoimmune responses remains unknown. This study assessed the potential of human Mreg to be used as an effective immunomodulatory method in xenotransplantation...
August 2, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28769554/the-modulation-of-enzyme-indoleamine-2-3-dioxygenase-from-dendritic-cells-for-the-treatment-of-type-1-diabetes-mellitus
#20
REVIEW
Débora Moitinho Abram, Luis Gustavo Romani Fernandes, Antônio Celso Saragossa Ramos Filho, Patrícia Ucelli Simioni
Diabetes mellitus type 1 (DM1) is an autoimmune disease in which β-cells of the pancreas islet are destroyed by T lymphocytes. Specific T cells are activated by antigen-presenting cells, mainly dendritic cells (DCs). It is already known that the regulation of tryptophan pathway in DC can be a mechanism of immunomodulation. The enzyme indoleamine 2,3-dioxygenase (IDO) is present in many cells, including DC, and participates in the metabolism of the amino acid tryptophan. Recent studies suggest the involvement of IDO in the modulation of immune response, which became more evident after the in vitro demonstration of IDO production by DC and of the ability of these cells to inhibit lymphocyte function through the control of tryptophan metabolism...
2017: Drug Design, Development and Therapy
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