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Tryptophan catabolism

Jean-Pierre Routy, Bertrand Routy, Gina M Graziani, Vikram Mehraj
The term "immune privilege" was originally coined to describe the suppression of inflammatory responses within organs protected by anatomic barriers, ie, the eyes, brain, placenta, and testes. However, cellular and metabolic processes, which orchestrate immune responses, also control inflammation within these sites. Our current understanding of tolerogenic mechanisms has extended the definition of immune privilege to include hair follicles, the colon, and cancer. By catabolizing tryptophan, cells expressing the enzyme indoleamine-2,3-dioxygenase produce kynurenine metabolites, which orchestrate local and systemic responses to control inflammation, thus maintaining immune privilege...
2016: International Journal of Tryptophan Research: IJTR
Auksė Zinkevičienė, Denis Kainov, Irutė Girkontaitė, Eglė Lastauskienė, Violeta Kvedarienė, Yu Fu, Simon Anders, Vidya Velagapudi
BACKGROUND: Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by repeated skin exposure to contact allergens. The severity and duration of this disease are associated with many different factors. Some of these factors may represent markers for monitoring disease activity and the individual response to an intervention. METHODS: We used a targeted metabolomics approach to find such factors in the serum of individuals with ACD. Metabolomics profiles were examined and compared in the acute phase of the disease and also in the absence of disease activity...
October 22, 2016: International Archives of Allergy and Immunology
Makedonka Gulcev, Cavan Reilly, Timothy J Griffin, Corey D Broeckling, Brian J Sandri, Bruce A Witthuhn, Shane W Hodgson, Prescott G Woodruff, Chris H Wendt
INTRODUCTION: Exacerbations are a leading cause of morbidity in COPD. The objective of this study was to identify metabolomic biomarkers of acute exacerbations of COPD (AECOPD). METHODS: We measured metabolites via mass spectrometry (MS) in plasma drawn within 24 hours of admission to the hospital for 33 patients with an AECOPD (day 0) and 30 days later and for 65 matched controls. Individual metabolites were measured via selective reaction monitoring with mass spectrometry...
2016: International Journal of Chronic Obstructive Pulmonary Disease
Cara C Schafer, Yong Wang, Kenneth P Hough, Anandi Sawant, Stefan C Grant, Victor J Thannickal, Jaroslaw Zmijewski, Selvarangan Ponnazhagan, Jessy S Deshane
Indoleamine 2,3-dioxygenase (IDO) has been implicated in immune evasion by tumors. Upregulation of this tryptophan (Trp)-catabolizing enzyme, in tumor cells and myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment (TME), leads to Trp depletion that impairs cytotoxic T cell responses and survival; however, exact mechanisms remain incompletely understood. We previously reported that a combination therapy of gemcitabine and a superoxide dismutase mimetic promotes anti-tumor immunity in a mouse model of lung cancer by inhibiting MDSCs, enhancing polyfunctional response of CD8+ memory T cells, and extending survival...
September 26, 2016: Oncotarget
Shardulendra Sherchand, Joyce A Ibana, Alison J Quayle, Ashok Aiyar
Chlamydia trachomatis is an obligate intracellular bacterial pathogen that cannot synthesize several amino acids, including tryptophan. Rather, C. trachomatis acquires these essential metabolites from its human host cell. Chlamydial dependence on host-provided tryptophan underlies a major host defense mechanism against the bacterium; namely, the induction of the host tryptophan-catabolizing enzyme, indoleamine 2,3- dioxygenase (IDO1) by interferon gamma (IFNγ), which leads to eradication of C. trachomatis by tryptophan starvation...
August 2016: Journal of Bacteriology & Parasitology
Michael B Cheung, Viviana Sampayo-Escobar, Ryan Green, Martin L Moore, Subhra Mohapatra, Shyam S Mohapatra
Respiratory syncytial virus (RSV) has been reported to infect human mesenchymal stem cells (MSCs) but the consequences are poorly understood. MSCs are present in nearly every organ including the nasal mucosa and the lung and play a role in regulating immune responses and mediating tissue repair. We sought to determine whether RSV infection of MSCs enhances their immune regulatory functions and contributes to RSV-associated lung disease. RSV was shown to replicate in human MSCs by fluorescence microscopy, plaque assay, and expression of RSV transcripts...
2016: PloS One
Ning Na, Yun Luo, Daqiang Zhao, Shicong Yang, Liangqing Hong, Heng Li, Bin Miao, Jiang Qiu
Immature dendritic cells (iDCs) are bone marrow-derived professional antigen-presenting cells, exhibit very low levels of the co-stimulatory molecules CD80 (B7-1), CD86 (B7-2), and CD40 and major histocompatibility complex (MHC) class II and play a critical role in triggering antigen-specific immunotolerance. The enzyme indoleamine 2, 3-dioxygenase (IDO) is a cytosolic tryptophan catabolism rate-limiting step enzyme. IDO secreted by DCs shows an association with the suppression of T-cell responses and promotion of tolerance...
September 27, 2016: Molecular Immunology
Mohammad-Ali Jenabian, Cecilia T Costiniuk, Vikram Mehraj, Feras M Ghazawi, Rémi Fromentin, Joëlle Brousseau, Pierre Brassard, Maud Bélanger, Petronela Ancuta, Reina Bendayan, Nicolas Chomont, Jean-Pierre Routy
OBJECTIVE: HIV persistence in long-lived infected cells and in anatomical sanctuary sites are major hurdles to HIV eradication. Testicular tissue may represent a significant viral sanctuary site as it constitutes an immunologically-privileged compartment. We assessed immuno-tolerance properties of the testicular tissue in individuals receiving suppressive ART. DESIGN AND METHODS: Testicular tissue and matched blood samples were collected from 6 virally suppressed adults and 10 HIV-uninfected controls prior to gender reassignment surgery...
September 24, 2016: AIDS
Judit Herédi, Anikó Magyariné Berkó, Ferenc Jankovics, Tokuko Iwamori, Naoki Iwamori, Etsuro Ono, Szatmár Horváth, Zsolt Kis, József Toldi, László Vécsei, Levente Gellért
During catabolism of tryptophan through the kynurenine (KYN) pathway, several endogenous metabolites with neuromodulatory properties are produced, of which kynurenic acid (KYNA) is one of the highest significance. The causal role of altered KYNA production has been described in several neurodegenerative and neuropsychiatric disorders (e.g., Parkinson's disease, Huntington's disease, schizophrenia) and therefore kynurenergic manipulation with the aim of therapy has recently been proposed. Conventionally, KYNA is produced from its precursor L-KYN with the aid of the astrocytic kynurenine aminotransferase-2 (KAT-2) in the murine brain...
August 27, 2016: Brain Structure & Function
Joerg C Schefold, Nora Fritschi, Gerhard Fusch, Aldin Bahonjic, Wolfram Doehner, Stephan von Haehling, Rene Pschowski, Christian Storm, Tim Schroeder
BACKGROUND/AIMS: Temperature control improves neurological prognosis in comatose cardiac arrest (CA) survivors. Previous reports demonstrate that most affected patients show signs of significant systemic inflammation. In an effort to better characterize potential temperature-related effects on key inflammatory pathways, we investigate the course of Tryptophan (Trp) levels, Tryptophan catabolites (including kynurenines) and indoleamine-2,3-dioxygenase (IDO)-activity in post CA patients...
October 2016: Resuscitation
Martyn Inman, Catarina Carvalho, William Lewis, Christopher J Moody
Annulin B, isolated from the marine hydroid isolated from Garveia annulata, is a potent inhibitor of the tryptophan catabolizing enzyme indoleamine-2,3-dioxygenase (IDO). A synthesis of the reported pyranonaphthoquinone structure is described, in which the key step is a regioselective Diels-Alder reaction between a pyranobenzoquinone dienophile and a silyl ketene acetal diene.
September 2, 2016: Journal of Organic Chemistry
Nady Braidy, Helene Rossez, Chai K Lim, Bat-Erdene Jugder, Bruce J Brew, Gilles J Guillemin
The kynurenine (KYN) pathway (KP) is a major degradative pathway of the amino acid, L-tryptophan (TRP), that ultimately leads to the anabolism of the essential pyridine nucleotide, nicotinamide adenine dinucleotide. TRP catabolism results in the production of several important metabolites, including the major immune tolerance-inducing metabolite KYN, and the neurotoxin and excitotoxin quinolinic acid. Dendritic cells (DCs) have been shown to mediate immunoregulatory roles that mediated by TRP catabolism. However, characterization of the KP in human DCs has so far only been partly delineated...
November 2016: Neurotoxicity Research
Vy Lam, Jidong Su, Anna Hsu, Garrett J Gross, Nita H Salzman, John E Baker
Intestinal microbiota determine severity of myocardial infarction in rats. We determined whether low molecular weight metabolites derived from intestinal microbiota and transported to the systemic circulation are linked to severity of myocardial infarction. Plasma from rats treated for seven days with the non-absorbed antibiotic vancomycin or a mixture of streptomycin, neomycin, polymyxin B and bacitracin was analyzed using mass spectrometry-based metabolite profiling platforms. Antibiotic-induced changes in the abundance of individual groups of intestinal microbiota dramatically altered the host's metabolism...
2016: PloS One
Sanaz Salehi, Kevin Howe, John Brooks, Mark L Lawrence, R Hartford Bailey, Attila Karsi
BACKGROUND: Regardless of sanitation practices implemented to reduce Salmonella prevalence in poultry processing plants, the problem continues to be an issue. To gain an understanding of the attachment mechanism of Salmonella to broiler skin, a bioluminescent-based mutant screening assay was used. A random mutant library of a field-isolated bioluminescent strain of Salmonella enterica serovar Kentucky was constructed. Mutants' attachment to chicken skin was assessed in 96-well plates containing uniform 6 mm diameter pieces of circular chicken skin...
2016: BMC Microbiology
Perrine Bortolotti, Benjamin Hennart, Camille Thieffry, Guillaume Jausions, Emmanuel Faure, Teddy Grandjean, Marion Thepaut, Rodrigue Dessein, Delphine Allorge, Benoit P Guery, Karine Faure, Eric Kipnis, Bertrand Toussaint, Audrey Le Gouellec
BACKGROUND: Pseudomonas aeruginosa (Pa) is a Gram-negative bacteria frequently involved in healthcare-associated pneumonia with poor clinical outcome. To face the announced post-antibiotic era due to increasing resistance and lack of new antibiotics, new treatment strategies have to be developed. Immunomodulation of the host response involved in outcome could be an alternative therapeutic target in Pa-induced lung infection. Kynurenines are metabolites resulting from tryptophan catabolism and are known for their immunomodulatory properties...
2016: BMC Microbiology
Yoshiji Ohta, Hisako Kubo, Koji Yashiro, Koji Ohashi, Yuji Tsuzuki, Naoya Wada, Yasuko Yamamoto, Kuniaki Saito
The aim of this study was to clarify the effect of water-immersion restraint stress (WIRS) on tryptophan (Trp) catabolism through the kynurenine (Kyn) pathway in rat tissues. The tissues of rats subjected to 6 h of WIRS (+WIRS) had increased tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) activities and increased TDO and IDO1 (one of two IDO isozymes in mammals) mRNA expression levels, with decreased Trp and increased Kyn contents in the liver. +WIRS rats had unchanged TDO and IDO activities in the kidney, decreased TDO activity and unchanged IDO activity in the brain, and unchanged IDO activity in the lung and spleen, with increased Kyn content in all of these tissues...
June 30, 2016: Journal of Physiological Sciences: JPS
Xavier Dagenais-Lussier, Mouna Aounallah, Vikram Mehraj, Mohamed El-Far, Cecile Tremblay, Rafick-Pierre Sekaly, Jean-Pierre Routy, Julien van Grevenynghe
UNLABELLED: Early HIV-1 infection is characterized by enhanced tryptophan catabolism, which contributes to immune suppression and disease progression. However, the mechanism by which kynurenine, a tryptophan-related metabolite, induces immune suppression remains poorly understood. Herein, we show that the increased production of kynurenine correlates with defective interleukin-2 (IL-2) signaling in memory CD4 T cells from HIV-infected subjects. Defective IL-2 signaling in these subjects, which drives reduced protection from Fas-mediated apoptosis, was also associated with memory CD4 T-cell loss...
September 1, 2016: Journal of Virology
Anil Kumar Nalini Chandran, Ryza A Priatama, Vikranth Kumar, Yuanhu Xuan, Byoung Il Je, Chul Min Kim, Ki-Hong Jung, Chang-Deok Han
Nitrogen (N) is the most important macronutrient for plant growth and grain yields. For rice crops, nitrate and ammonium are the major N sources. To explore the genomic responses to ammonium supplements in rice roots, we used 17-day-old seedlings grown in the absence of external N that were then exposed to 0.5mM (NH4)2SO4 for 3h. Transcriptomic profiles were examined by microarray experiments. In all, 634 genes were up-regulated at least two-fold by the N-supplement when compared with expression in roots from untreated control plants...
August 1, 2016: Journal of Plant Physiology
B C Guard, J S Suchodolski
Recent molecular studies have revealed a complex microbiota in the dog intestine. Convincing evidence has been reported linking changes in microbial communities to acute and chronic gastrointestinal inflammation, especially in canine inflammatory bowel disease (IBD). The most common microbial changes observed in intestinal inflammation are decreases in the bacterial phyla Firmicutes (i.e., Lachnospiraceae, Ruminococcaceae, and ) and Bacteroidetes, with concurrent increases in Proteobacteria (i.e., ). Due to the important role of microbial-derived metabolites for host health, it is important to elucidate the metabolic consequences of gastrointestinal dysbiosis and physiological pathways implicated in specific disease phenotypes...
June 2016: Journal of Animal Science
J Jacques Matte, Etienne Corrent, Aude Simongiovanni, Nathalie Le Floc'h
The present experiment aimed to determine if Trp metabolism and growth responses to dietary Trp are modulated by dietary niacin (B) in weanling piglets. Piglets weaned at 3 wk of age were distributed 1 wk later (7.6 kg of BW, SEM = 0.1) in 52 pens of 2 animals each. Pens were assigned to factorial dietary treatments with 2 additions of B, 15 mg/kg (LB3) vs. 45 mg/kg (HB3) and 2 additions of Trp, 0 mg/kg (-Trp) vs. 1 mg/kg (+Trp) for Trp to Lys ratios of 0.16 vs. 0.24, respectively. Growth performance was recorded every week from 4 to 10 wk of age...
May 2016: Journal of Animal Science
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