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Indoleamine 2,3-dioxygenase

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https://www.readbyqxmd.com/read/28214225/a-relay-pathway-between-arginine-and-tryptophan-metabolism-confers-immunosuppressive-properties-on-dendritic-cells
#1
Giada Mondanelli, Roberta Bianchi, Maria Teresa Pallotta, Ciriana Orabona, Elisa Albini, Alberta Iacono, Maria Laura Belladonna, Carmine Vacca, Francesca Fallarino, Antonio Macchiarulo, Stefano Ugel, Vincenzo Bronte, Federica Gevi, Lello Zolla, Auke Verhaar, Maikel Peppelenbosch, Emilia Maria Cristina Mazza, Silvio Bicciato, Yasmina Laouar, Laura Santambrogio, Paolo Puccetti, Claudia Volpi, Ursula Grohmann
Arginase 1 (Arg1) and indoleamine 2,3-dioxygenase 1 (IDO1) are immunoregulatory enzymes catalyzing the degradation of l-arginine and l-tryptophan, respectively, resulting in local amino acid deprivation. In addition, unlike Arg1, IDO1 is also endowed with non-enzymatic signaling activity in dendritic cells (DCs). Despite considerable knowledge of their individual biology, no integrated functions of Arg1 and IDO1 have been reported yet. We found that IDO1 phosphorylation and consequent activation of IDO1 signaling in DCs was strictly dependent on prior expression of Arg1 and Arg1-dependent production of polyamines...
February 13, 2017: Immunity
https://www.readbyqxmd.com/read/28212884/desipramine-decreases-expression-of-human-and-murine-indoleamine-2-3-dioxygenases
#2
Alexandra K Brooks, Tiffany M Janda, Marcus A Lawson, Jennifer L Rytych, Robin A Smith, Cecilia Ocampo-Solis, Robert H McCusker
Abundant evidence connects depression symptomology with immune system activation, stress and subsequently elevated levels of kynurenine. Anti-depressants, such as the tricyclic norepinephrine/serotonin reuptake inhibitor desipramine (Desip), were developed under the premise that increasing extracellular neurotransmitter level was the sole mechanism by which they alleviate depressive symptomologies. However, evidence suggests that anti-depressants have additional actions that contribute to their therapeutic potential...
February 14, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28212441/depressive-disorder-and-gastrointestinal-dysfunction-after-myocardial-infarct-are-associated-with-abnormal-tryptophan-5-hydroxytryptamine-metabolism-in-rats
#3
Xiaofang Lu, Yuefen Wang, Chunyan Liu, Yangang Wang
In this study, we investigated the relationship between tryptophan-5-hydroxytryptamine metabolism, depressive disorder, and gastrointestinal dysfunction in rats after myocardial infarction. Our goal was to elucidate the physiopathologic bases of somatic/psychiatric depression symptoms after myocardial infarction. A myocardial infarction model was established by permanent occlusion of the left anterior descending coronary artery. Depression-like behavior was evaluated using the sucrose preference test, open field test, and forced swim test...
2017: PloS One
https://www.readbyqxmd.com/read/28201999/effect-of-myeloid-differentiation-primary-response-gene-88-on-expression-profiles-of-genes-during-the-development-and-progression-of-helicobacter-induced-gastric-cancer
#4
Ivonne Lozano-Pope, Arnika Sharma, Michael Matthias, Kelly S Doran, Marygorret Obonyo
BACKGROUND: Gastric cancer is one of the most common and lethal type of cancer worldwide. Infection with Helicobacter pylori (H. pylori) is recognized as the major cause of gastric cancer. However, it remains unclear the mechanism by which Helicobacter infection leads to gastric cancer. Furthermore, the underlying molecular events involved during the progression of Helicobacter infection to gastric malignancy are not well understood. In previous studies, we demonstrated that that H. felis-infected Myd88 (-/-) mice exhibited dramatic pathology and an accelerated progression to gastric dysplasia; however, the MyD88 downstream gene targets responsible for this pathology have not been described...
February 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28198424/human-ido-competent-long-lived-immunoregulatory-dendritic-cells-induced-by-intracellular-pathogen-and-their-fate-in-humanized-mice
#5
Rajeev K Tyagi, Brodie Miles, Rajesh Parmar, Neeraj K Garg, Sarat K Dalai, Babak Baban, Christopher W Cutler
Targeting of myeloid-dendritic cell receptor DC-SIGN by numerous chronic infectious agents, including Porphyromonas gingivalis, is shown to drive-differentiation of monocytes into dysfunctional mDCs. These mDCs exhibit alterations of their fine-tuned homeostatic function and contribute to dysregulated immune-responses. Here, we utilize P. gingivalis mutant strains to show that pathogen-differentiated mDCs from primary human-monocytes display anti-apoptotic profile, exhibited by elevated phosphorylated-Foxo1, phosphorylated-Akt1, and decreased Bim-expression...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28191010/role-of-dietary-metabolites-in-regulating-the-host-immune-response-in-gastrointestinal-disease
#6
REVIEW
Mohamad El-Zaatari, John Y Kao
The host immune response to gastrointestinal (GI) infections, hypersensitivity reactions, or GI cancers comprises numerous pathways that elicit responses on different host cells. Some of these include (1) the stimulation of mast cells via their IgE receptor, (2) the production of antibodies leading to antibody-mediated cytotoxic T/natural killer cell killing, (3) the activation of the complement pathway, and (4) the activation of the adaptive immune response via antigen-presenting cell, T cell, and B cell interactions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28179106/non-tumor-cell-ido1-predominantly-contributes-to-enzyme-activity-and-response-to-ctla-4-pd-l1-inhibition-in-mouse-glioblastoma
#7
Lijie Zhai, Erik Ladomersky, Carlos R Dostal, Kristen Lauing, Kathleen Swoap, Leah K Billingham, Galina Gritsina, Meijing Wu, Robert H McCusker, David C Binder, Derek A Wainwright
Glioblastoma (GBM) is the most common malignant brain tumor in adults with a median survival of 14.6 months. A contributing factor to GBM aggressiveness is the intratumoral expression of the potently immunosuppresive enzyme, indoleamine 2,3 dioxygenase 1 (IDO1). The enzymatic activity of IDO1 is associated with the conversion of tryptophan into downstream kynurenine (Kyn), which has previously been hypothesized to contribute toward the suppression of tumor immunity. Utilizing the syngeneic, immunocompetent, intracranial GL261 cell GBM model, we previously demonstrated that tumor cell-, but not non-tumor cell-IDO1, suppresses T cell-mediated brain tumor regression in mice...
February 4, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28176942/nanomedicine-and-cancer-immunotherapy-focus-on-indoleamine-2-3-dioxygenase-inhibitors
#8
REVIEW
Bilal Zulfiqar, Amnah Mahroo, Kaenat Nasir, Rai Khalid Farooq, Nasir Jalal, Muhammad Usman Rashid, Kashif Asghar
Nanomedicine application in cancer immunotherapy is currently one of the most challenging areas in cancer therapeutic intervention. Innovative solutions have been provided by nanotechnology to deliver cytotoxic agents to the cancer cells partially affecting the healthy cells of the body during the process. Nanoparticle-based drug delivery is an emerging approach to stimulate the immune responses against cancer. The inhibition of indoleamine 2,3-dioxygenase (IDO) is a pivotal area of research in cancer immunotherapy...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28170190/enhanced-immunosuppression-of-t-cells-by-sustained-presentation-of-bioactive-interferon-%C3%AE-within-three-dimensional-mesenchymal-stem-cell-constructs
#9
Joshua A Zimmermann, Marian H Hettiaratchi, Todd C McDevitt
The immunomodulatory activity of mesenchymal stem/stromal cells (MSCs) to suppress innate and adaptive immune responses offers a potent cell therapy for modulating inflammation and promoting tissue regeneration. However, the inflammatory cytokine milieu plays a critical role in stimulating MSC immunomodulatory activity. In particular, interferon-γ (IFN-γ)-induced expression of indoleamine 2,3-dioxygenase (IDO) is primarily responsible for MSC suppression of T-cell proliferation and activation. Although pretreatment with IFN-γ is commonly used to prime MSCs for immunomodulatory activity prior to transplantation, the transient effects of pretreatment may limit the potential of MSCs to potently modulate immune responses...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28167776/tgf-%C3%AE-inhibitor-smad7-regulates-dendritic-cell-induced-autoimmunity
#10
Dominika Lukas, Nir Yogev, Junda M Kel, Tommy Regen, Ilgiz A Mufazalov, Yilang Tang, Florian Wanke, Boris Reizis, Werner Müller, Florian C Kurschus, Marco Prinz, Ingo Kleiter, Björn E Clausen, Ari Waisman
TGF-β is an anti-inflammatory cytokine whose signaling is negatively controlled by Smad7. Previously, we established a role for Smad7 in the generation of autoreactive T cells; however, the function of Smad7 in dendritic cells (DCs) remains elusive. Here, we demonstrate that DC-specific Smad7 deficiency resulted in elevated expression of the transcription factors Batf3 and IRF8, leading to increased frequencies of CD8(+)CD103(+) DCs in the spleen. Furthermore, Smad7-deficient DCs expressed higher levels of indoleamine 2,3-dioxygenase (IDO), an enzyme associated with tolerance induction...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28155213/intracerebroventricular-administration-of-streptozotocin-as-an-experimental-approach-to-depression-evidence-for-the-involvement-of-proinflammatory-cytokines-and-indoleamine-2-3-dioxygenase
#11
Leandro Cattelan Souza, Cristiano R Jesse, Marcelo Gomes de Gomes, Cristini Escobar Viana, Etiara Mattos, Neici Cáceres Silva, Silvana Peterini Boeira
There is a lack of information about the molecular events underlying the depressive-like effect of an intracerebroventricular injection of streptozotocin (ICV-STZ) in mice. Elevated activity of the tryptophan-degrading enzyme indoleamine-2,3-dioxygenase (IDO) has been proposed to mediate depression in inflammatory disorders. In this study, we report that ICV-STZ activates IDO in the hippocampus of mice and culminates in depressive-like behaviors, measured by an increased duration in immobility time in the forced swimming test and decreased total time of grooming in the splash test...
February 2, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28142215/proteasomal-ido-degradation-reduces-the-immunosuppressive-potential-of-clinical-grade-mesenchymal-stromal-cells-undergoing-replicative-senescence
#12
Séverine Loisel, Joëlle Dulong, Cédric Ménard, Marie-Laure Renoud, Nadine Meziere, Bezier Isabelle, Maëlle Latour, Nadège Bescher, Rémy Pedeux, Nicolas Bertheuil, Erwan Flecher, Luc Sensebé, Karin Tarte
Owing to their immunosuppressive properties, mesenchymal stromal cells (MSCs) obtained from bone marrow (BM-MSCs) or adipose tissue (ASCs) are considered a promising tool for cell therapy. However, important issues should be considered to ensure the reproducible production of efficient and safe clinical-grade MSCs. In particular, high expansion rate, associated with progressive senescence, was recently proposed as one of the parameters that could alter MSC functionality. In this study, we directly address the consequences of replicative senescence on BM-MSC and ASC immunomodulatory properties...
January 31, 2017: Stem Cells
https://www.readbyqxmd.com/read/28140445/virulence-dependent-induction-of-interleukin-10-producing-tolerogenic-dendritic-cells-by-mycobacterium-tuberculosis-impedes-optimal-th1-proliferation
#13
Hongmin Kim, Kee Woong Kwon, Woo Sik Kim, Sung Jae Shin
Mycobacterium tuberculosis (Mtb) inhibits optimal Th1 responses during infection. However, the precise mechanisms by which virulent Mtb limits Th1 responses remain unclear. Here, we infected dendritic cells (DCs) with the virulent Mtb strain H37Rv or the attenuated strain H37Ra to investigate the phenotypic and functional alterations in DCs and resultant T cell responses. H37Rv-infected DCs suppressed Th1 responses more strongly than H37Ra-infected DCs. Interestingly, H37Rv, but not H37Ra, impaired DC surface molecule (CD80, CD86 and MHC class II) expression due to prominent IL-10 production while augmenting the expression of tolerogenic molecules including PD-L1, CD103, Tim-3, and indoleamine 2,3-dioxygenase (IDO) on DCs in a multiplicity-of-infection-dependent manner...
January 31, 2017: Immunology
https://www.readbyqxmd.com/read/28138019/involvement-of-host-defense-mechanisms-against-toxoplasma-gondii-infection-in-anhedonic-and-despair-like-behaviors-in-mice
#14
Motamed E Mahmoud, Ragab Fereig, Yoshifumi Nishikawa
Toxoplasma gondii is a pathogen relevant to psychiatric disorders. We recently showed that reactivation of chronic T. gondii induced depressive-like behaviors in mice. Further, it has been hypothesized that depression-like behaviors are mediated via a host defense mechanism against invading pathogens; proximate mechanisms of this behavioral hypothesis remain unclear. In the present study, we investigate the contribution of indoleamine 2, 3-dioxygenase (IDO), inflammation and interferon-gamma (IFN-γ) on anhedonic- and despair-related behaviors in T...
January 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28132869/bone-marrow-derived-mesenchymal-stromal-cells-from-sickle-cell-disease-patients-display-intact-functionality
#15
Elizabeth O Stenger, Raghavan Chinnadurai, Shala Yuan, Marco Garcia, Dalia Arafat, Greg Gibson, Lakshmanan Krishnamurti, Jacques Galipeau
Hematopoietic cell transplantation (HCT) is the only cure for sickle cell disease (SCD), but engraftment remains challenging in patients lacking matched donors. Infusion of mesenchymal stromal cells (MSCs) at time of HCT may promote hematopoiesis and ameliorate graft-versus-host disease. Experimental murine models suggest MSC major histocompatibility complex compatibility with recipient impacts their in vivo function, suggesting autologous MSCs could be superior to third-party MSCs for promoting HCT engraftment...
January 26, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28132413/immunotolerant-indoleamine-2-3-dioxygenase-increases-in-condyloma-acuminata
#16
Z Xie, M Zhang, W Xiong, H Y Wan, X C Zhao, T Xie, H Lei, Z C Lin, D S Luo, X L Liang, Y H Chen
BACKGROUND: The tryptophan-depleting enzyme indoleamine-2,3-dioxygenase (IDO) is critical for the regulation of immune tolerance and plays an important role in immune-associated skin diseases. OBJECTIVES: To analyze the level of IDO in condyloma acuminata (CA) and its role in this condition. METHODS: IDO expression was assessed in the skin and peripheral blood of healthy subjects and patients with CA. To assess the role of skin IDO in immunity, the ability of isolated epidermal cells to metabolize tryptophan and the influence on polyclonal T cell mitogen (PHA)-stimulated T cell proliferation were explored...
January 29, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28131097/downregulation-of-indoleamine-2-3-dioxygenase-expression-in-the-villous-stromal-endothelial-cells-of-placentas-with-preeclampsia
#17
Naoyuki Iwahashi, Madoka Yamamoto, Sakiko Nanjo, Saori Toujima, Sawako Minami, Kazuhiko Ino
INTRODUCTION: Previous studies have shown that indoleamine 2, 3-dioxygenase (IDO), an immunosuppressive enzyme that converts tryptophan to kynurenine, is expressed in the placenta and might play a role in the maintenance of pregnancy, although its associations with the pathogeneses of preeclampsia (PE) and fetal growth restriction (FGR) remain unclear. The objective of this study was to investigate the differences in IDO expression among normal, PE, and FGR placentas, and the associations between IDO expression and clinical symptoms, or the expression of fms-like tyrosine kinase receptor-1 (Flt-1)...
January 23, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/28129624/erianin-inhibits-indoleamine-2-3-dioxygenase-induced-tumor-angiogenesis
#18
Chang Su, Peng Zhang, Jianwen Liu, Yiou Cao
Tumor angiogenesis is the key process in tumor growth and metastasis, and transfers essential nutrients for solid tumor. Inhibition of tumor angiogenesis has been recognized as a more effective anti-cancer strategy for NSCLC and has acquired certain therapeutic effects. IDO has non-immune functions including regulating tumor angiogenesis and IDO dysregulation in cancer pathogenesis has been valued. Erianin is a natural product isolated from Dendrobium chrysotoxum Lindl. The antitumor activity of erianin in many kinds of cancers had been demonstrated in previous studies...
January 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28123606/strong-correlation-of-indoleamine-2-3-dioxygenase-1-expression-with-basal-like-phenotype-and-increased-lymphocytic-infiltration-in-triple-negative-breast-cancer
#19
Sewha Kim, Sanghui Park, Min Sun Cho, Woosung Lim, Byung-In Moon, Sun Hee Sung
Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme involved in tumor immune escape. Blockade of the IDO1 pathway is an emerging modality of cancer immunotherapy. Triple-negative breast cancer (TNBC) lacks established therapeutic targets and may be a good candidate for this novel immunotherapeutic agent. The purpose of this study was to evaluate the clinicopathologic characteristics of the IDO1-expressing TNBC subset. A tissue microarray was constructed from 200 patients with TNBC. Immunohistochemistry (IHC) for IDO1 and TNBC molecular subtype-surrogate markers (AR, GCDFP-15, claudin-3, E-cadherin, CK5/6, and EGFR) was performed using this tissue microarray...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28123064/guanylate-binding-protein-1-gbp1-contributes-to-the-immunity-of-human-mesenchymal-stromal-cells-against-toxoplasma-gondii
#20
Aiping Qin, De-Hua Lai, Qifa Liu, Weijun Huang, Ya-Ping Wu, Xiaoyong Chen, Sunxing Yan, Huimin Xia, Geoff Hide, Zhao-Rong Lun, Francisco J Ayala, Andy Peng Xiang
Mesenchymal stromal cells (MSCs) have recently been shown to play important roles in mammalian host defenses against intracellular pathogens, but the molecular mechanism still needs to be clarified. We confirmed that human MSCs (hMSCs) prestimulated with IFN-γ showed a significant and dose-dependent ability to inhibit the growth of two types of Toxoplasma gondii [type I RH strain with green fluorescent proteins (RH/GFP) or type II PLK strain with red fluorescent proteins (PLK/RED)]. However, in contrast to previous reports, the anti-T...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
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