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multiple sclerosis and IDO

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https://www.readbyqxmd.com/read/27540379/current-evidence-for-a-role-of-the-kynurenine-pathway-of-tryptophan-metabolism-in-multiple-sclerosis
#1
REVIEW
Michael D Lovelace, Bianca Varney, Gayathri Sundaram, Nunzio F Franco, Mei Li Ng, Saparna Pai, Chai K Lim, Gilles J Guillemin, Bruce J Brew
The kynurenine pathway (KP) is the major metabolic pathway of the essential amino acid tryptophan (TRP). Stimulation by inflammatory molecules, such as interferon-γ (IFN-γ), is the trigger for induction of the KP, driving a complex cascade of production of both neuroprotective and neurotoxic metabolites, and in turn, regulation of the immune response and responses of brain cells to the KP metabolites. Consequently, substantial evidence has accumulated over the past couple of decades that dysregulation of the KP and the production of neurotoxic metabolites are associated with many neuroinflammatory and neurodegenerative diseases, including Parkinson's disease, AIDS-related dementia, motor neurone disease, schizophrenia, Huntington's disease, and brain cancers...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/26995730/recent-evidence-for-an-expanded-role-of-the-kynurenine-pathway-of-tryptophan-metabolism-in-neurological-diseases
#2
REVIEW
Michael D Lovelace, Bianca Varney, Gayathri Sundaram, Matthew J Lennon, Chai K Lim, Kelly Jacobs, Gilles J Guillemin, Bruce J Brew
The kynurenine pathway (KP) of tryptophan metabolism has emerged in recent years as a key regulator of the production of both neuroprotective (e.g. kynurenic and picolinic acid, and the essential cofactor NAD+) and neurotoxic metabolites (e.g. quinolinic acid, 3-hydroxykynurenine). The balance between the production of the two types of metabolites is controlled by key rate-limiting enzymes such as indoleamine-2,3-dioxygenase (IDO-1), and in turn, molecular signals such as interferon-γ (IFN-γ), which activate the KP metabolism of tryptophan by this enzyme, as opposed to alternative pathways for serotonin and melatonin production...
January 2017: Neuropharmacology
https://www.readbyqxmd.com/read/26365612/ebv-and-vitamin-d-status-in-relapsing-remitting-multiple-sclerosis-patients-with-a-unique-cytokine-signature
#3
Ahmad Nejati, Zabihollah Shoja, Shohreh Shahmahmoodi, Abbas Tafakhori, Yaghoub Mollaei-Kandelous, Farhad Rezaei, Kabir Magaji Hamid, Abbas Mirshafiey, Rozita Doosti, Mohammad Ali Sahraian, Mahmood Mahmoudi, Fazel Shokri, Vince Emery, Sayed Mahdi Marashi
Multiple sclerosis, a debilitating autoimmune and inflammatory disease of the central nervous system, is associated with both infectious and non-infectious factors. We investigated the role of EBV infection, vitamin D level, and cytokine signature in MS patients. Molecular and serological assays were used to investigate immune biomarkers, vitamin D level, and EBV status in 83 patients with relapsing-remitting multiple sclerosis and 62 healthy controls. In total, 98.8 % of MS patients showed a history of EBV exposure compared to 88...
April 2016: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/26110930/indoleamine-2-3-dioxygenase-ido-expression-and-activity-in-relapsing-remitting-multiple-sclerosis
#4
Roberta Mancuso, Ambra Hernis, Simone Agostini, Marco Rovaris, Domenico Caputo, Dietmar Fuchs, Mario Clerici
BACKGROUND: Interferon gamma (IFN-γ) production induces the transcription of indoleamine 2,3 dioxygenase (IDO) resulting in the reduction of T-cell activation and proliferation through the depletion of tryptophan and the elicitation of Treg lymphocytes. IDO was shown to be involved in the pathogenesis of autoimmune diseases; we investigated whether changes in IDO gene expression and activity could be indicative of onset of relapse in multiple sclerosis (MS) patients. METHODS: IDO and interferon-γ (IFN-γ) gene expression, serum IDO activity (Kynurenine/Tryptophan ratio) and serum neopterin concentration--a protein released by macrophages upon IFN-γ stimulation--were measured in 51 individuals: 36 relapsing remitting (RR)-MS patients (21 in acute phase--AMS, 15 in stable phase--SMS) and 15 healthy controls (HC)...
2015: PloS One
https://www.readbyqxmd.com/read/24362236/gcn2-kinase-plays-an-important-role-triggering-the-remission-phase-of-experimental-autoimmune-encephalomyelitis-eae-in-mice
#5
Heloisa Orsini, Leandro P Araujo, Juliana T Maricato, Marcia G Guereschi, Mario Mariano, Beatriz A Castilho, Alexandre S Basso
Experimental autoimmune encephalomyelitis (EAE) has been widely employed as a model to study multiple sclerosis (MS) and indeed has allowed some important advances in our comprehension of MS pathogenesis. Several pieces of evidence suggest that infiltrating Th1 and Th17 lymphocytes are important players leading to CNS demyelination and lesion during the peak of murine EAE. Subsequently, effector T cell responses rapidly decline and the recovery phase of the disease strongly correlates with the expression of anti-inflammatory cytokines and the enrichment of Foxp3+ regulatory T (Treg) cells within the target organ...
March 2014: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/23993943/tryptophan-metabolite-analog-n-3-4-dimethoxycinnamonyl-anthranilic-acid-ameliorates-acute-graft-versus-host-disease-through-regulating-t-cell-proliferation-and-polarization
#6
Jinhuan Xu, Jia Wei, Min Huang, Xianmin Zhu, Jun Guan, Jin Yin, Yi Xiao, Yicheng Zhang
Local catabolism of tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is considered an important mechanism of regulating T cell immunity. N-(3,4-dimethoxycinnamonyl) anthranilic acid (3,4-DAA) is an active synthetic anthranilic acid derivative which was proved to be effective to treat type1helper T lymphocyte (Th1) mediated autoimmune diseases such as multiple sclerosis. In this report, we investigated the effects of 3,4-DAA on the acute graft versus host disease (aGVHD) following allogeneic bone marrow transplantation (allo-BMT) and its potential mechanism of action...
November 2013: International Immunopharmacology
https://www.readbyqxmd.com/read/23805274/cd8-t-cells-are-required-for-glatiramer-acetate-therapy-in-autoimmune-demyelinating-disease
#7
Andrew F Tyler, Jason P Mendoza, Mihail Firan, Nitin J Karandikar
The exact mechanism of glatiramer acetate (GA, Copaxone®), an FDA-approved immunomodulatory therapy for multiple sclerosis (MS), remains unclear after decades of research. Previously, we have shown that GA therapy of MS induces CD8(+) T cell responses that can potentially suppress pathogenic CD4(+) T cell responses. Using a murine model of MS, experimental autoimmune encephalomyelitis (EAE), we now demonstrate that CD8(+) T cells are necessary in mediating the therapeutic effects of GA. Further, adoptive transfer of GA-induced CD8(+) T cells resulted in amelioration of EAE, establishing a role as a viable immunotherapy in demyelinating disease...
2013: PloS One
https://www.readbyqxmd.com/read/23521914/vitamin-d3-induces-ido-tolerogenic-dcs-and-enhances-treg-reducing-the-severity-of-eae
#8
Alessandro S Farias, Gabriela S Spagnol, Pedro Bordeaux-Rego, Camila O F Oliveira, Ana Gabriela M Fontana, Rosemeire F O de Paula, Mariana P A Santos, Fernando Pradella, Adriel S Moraes, Elaine C Oliveira, Ana Leda F Longhini, Alexandre C S Rezende, Mauro W Vaisberg, Leonilda M B Santos
BACKGROUND: A growing body of evidence supports the hypothesis that vitamin D is an important environmental factor in the etiology of T-cell-mediated autoimmune diseases such as multiple sclerosis (MS). AIM: The purpose of this study was exploring the mechanisms underlying the beneficial effect of vitamin D3 in encephalomyelitis (EAE). METHODS: We treated monophasic experimental autoimmune EAE, induced in Lewis rat, with vitamin D3 and adoptively transfer tolerogenic bone marrow-derived DCs generated in the presence of vitamin D3...
April 2013: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/22258797/the-role-of-kynurenines-in-the-pathomechanism-of-amyotrophic-lateral-sclerosis-and-multiple-sclerosis-therapeutic-implications
#9
REVIEW
Judit Füvesi, Cecilia Rajda, Krisztina Bencsik, József Toldi, László Vécsei
Tryptophan is one of the essential amino acids, 80% of which is catabolised in the extrahepatic tissues by indoleamine-2,3-dioxygenase (IDO), the rate-limiting enzyme of the kynurenine pathway. Metabolites along the kynurenine pathway have been implicated to play a role in the pathomechanism of neuroinflammatory and neurodegenerative disorders. Changes in the concentration levels of kynurenines can shift the balance to pathological conditions. The ability to influence the metabolism towards the neuroprotective branch of the kynurenine pathway, i...
February 2012: Journal of Neural Transmission
https://www.readbyqxmd.com/read/21723567/vitamin-d-mediated-immune-regulation-in-multiple-sclerosis
#10
Jorge Correale, María Célica Ysrraelit, María Inés Gaitán
Although Vitamin D is best known as a modulator of calcium homeostasis, it also has immune modulating potential. A protective effect of Vitamin D on Multiple Sclerosis (MS) is supported by the reduced risk associated with sun exposure and use of Vitamin D supplements. Moreover, high circulating levels of Vitamin D have been associated with lower risk of MS. To gain more insight into putative regulatory mechanisms of Vitamin D in MS pathogenesis, we studied 132 Hispanic patients with clinically definite MS, 58 with relapsing remitting MS (RR MS) during remission, 34 RR MS patients during relapse, and 40 primary progressive MS cases (PP MS)...
December 15, 2011: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/21118329/multiple-sclerosis-seizures-and-antiepileptics-role-of-il-18-ido-and-melatonin
#11
REVIEW
G Anderson, M Rodriguez
To review the treatment and mechanisms underlying the increased prevalence of seizures associated with multiple sclerosis (MS). We carried out an extensive review of the literature pertaining to seizures in MS. We propose that an increase in interleukin-18, and its associated induction of indoleamine 2, 3-dioxygenase and quinolinic acid, mediates seizure activity in MS at least in part via an increase in interferon-gamma (IFNg). Increased kynurenine pathway activity decreases the availability of serotonin and melatonin...
May 2011: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/21075457/regulation-of-th1-th17-cytokines-and-ido-gene-expression-by-inhibition-of-calpain-in-pbmcs-from-ms-patients
#12
Amena W Smith, Bently P Doonan, William R Tyor, Nada Abou-Fayssal, Azizul Haque, Naren L Banik
Multiple sclerosis (MS) pathology is marked by the massive infiltration of myelin-specific T cells into the central nervous system (CNS). During active disease, pro-inflammatory Th1/Th17 cells predominate over immunoregulatory Th2/Treg cells. Here, we show that calpain inhibition downregulates Th1/Th17 inflammatory cytokines and mRNA in MS patient peripheral blood mononuclear cells (PBMCs) activated with anti-CD3/28 or MBP. Interestingly, calpain inhibition elevated IDO gene expression in MS PBMCs, which was markedly decreased in calpain expressing cells...
March 2011: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/20437560/role-of-cd8-cd25-foxp3-regulatory-t-cells-in-multiple-sclerosis
#13
Jorge Correale, Andrés Villa
OBJECTIVE: The objective of this study was to investigate the role of CD8+ CD25+ FoxP3+ cells during the course of multiple sclerosis (MS). METHODS: Peripheral blood and cerebrospinal fluid (CSF) CD8+ T-cell clones (TCCs) recognizing autoreactive CD4+ T cells were isolated from 20 MS patients during exacerbations, 15 patients in remission, 15 healthy subjects, and 10 patients with other inflammatory neurological diseases. Characteristics of noncytotoxic CD8+ CD25+ regulatory T cells were studied...
May 2010: Annals of Neurology
https://www.readbyqxmd.com/read/20346490/increased-cannabinoid-receptor-1-immunoreactive-nerve-fibers-in-overactive-and-painful-bladder-disorders-and-their-correlation-with-symptoms
#14
COMPARATIVE STUDY
Gaurav Mukerji, Yiangos Yiangou, Sanjiv K Agarwal, Praveen Anand
OBJECTIVE: To study the expression of cannabinoid receptor 1 (CB1) in human urinary bladder hypersensitivity and overactivity disorders, and correlate changes with symptoms. Cannabinoid receptor agonists have been shown to modulate urinary bladder contractility and reduce pain after bladder inflammation; their clinical efficacy on lower urinary tract symptoms was demonstrated in the Cannabinoids in Multiple Sclerosis study. METHODS: Bladder tissue specimens were obtained from patients with painful bladder syndrome (PBS, n=13), idiopathic detrusor overactivity (IDO, n=14), and from controls with asymptomatic microscopic hematuria (n=16)...
June 2010: Urology
https://www.readbyqxmd.com/read/19461950/nicotinic-acid-mediated-activation-of-both-membrane-and-nuclear-receptors-towards-therapeutic-glucocorticoid-mimetics-for-treating-multiple-sclerosis
#15
W Todd Penberthy
Acute attacks of multiple sclerosis (MS) are most commonly treated with glucocorticoids, which can provide life-saving albeit only temporary symptomatic relief. The mechanism of action (MOA) is now known to involve induction of indoleamine 2,3-dioxygenase (IDO) and interleukin-10 (IL-10), where IL-10 requires subsequent heme oxygenase-1 (HMOX-1) induction. Ectopic expression studies reveal that even small changes in expression of IDO, HMOX-1, or mitochondrial superoxide dismutase (SOD2) can prevent demyelination in experimental autoimmune encephalomyelitis (EAE) animal models of MS...
2009: PPAR Research
https://www.readbyqxmd.com/read/19149604/the-importance-of-nad-in-multiple-sclerosis
#16
REVIEW
W Todd Penberthy, Ikuo Tsunoda
The etiology of multiple sclerosis (MS) is unknown but it manifests as a chronic inflammatory demyelinating disease in the central nervous system (CNS). During chronic CNS inflammation, nicotinamide adenine dinucleotide (NAD) concentrations are altered by (T helper) Th1-derived cytokines through the coordinated induction of both indoleamine 2,3-dioxygenase (IDO) and the ADP cyclase CD38 in pathogenic microglia and lymphocytes. While IDO activation may keep auto-reactive T cells in check, hyper-activation of IDO can leave neuronal CNS cells starving for extracellular sources of NAD...
2009: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/19067144/neuropsychiatric-disorders-related-to-interferon-and-interleukins-treatment
#17
REVIEW
Aye Mu Myint, Markus J Schwarz, Harry W M Steinbusch, Brian E Leonard
Certain cytokines such as interferon-alpha and interleukin-2 are often used in the treatment certain cancers and chronic diseases such as melanoma, hepatitis C infection and multiple sclerosis. Several neuropsychiatric side effects such as depression, anxiety, psychosis, suicidal ideation, hypomanic mood and cognitive impairment were reported in those patients who received those medications. In certain patients with those neuropsychiatric side effects, the symptoms ceased when the medication was stopped. However, in some cases, the cognitive impairment persisted even for years after cessation of the medication...
March 2009: Metabolic Brain Disease
https://www.readbyqxmd.com/read/18406591/emerging-concepts-in-cd8-t-regulatory-cells
#18
REVIEW
Jerry Y Niederkorn
CD8(+) T regulatory cells (T regs) are elicited by unique antigen presenting cells during viral infections, by manipulation of co-stimulatory molecules, or in the development of tumors. CD8(+) T regs display antigen-specificity, which is most exquisitely manifested by the HLA-E-restricted cytolytic CD8(+) T regs in MS. There is evidence that some CD8(+) T regs also express organ specificity. In many cases, IFN-gamma is required for either the induction or expression of CD8(+) T regs. CD8(+) T regs can produce suppression directly by killing immune cells or indirectly by co-opting other cells to elaborate end-stage suppressive molecules such as TGF-beta, IL-10, and indoleamine dioxygenase (IDO)...
June 2008: Current Opinion in Immunology
https://www.readbyqxmd.com/read/18077006/stem-cells-ameliorate-eae-via-an-indoleamine-2-3-dioxygenase-ido-mechanism
#19
Mariola Matysiak, Mariusz Stasiołek, Wojciech Orłowski, Anna Jurewicz, Szymon Janczar, Cedric S Raine, Krzysztof Selmaj
Syngeneic, pluripotent Lin(-)Sca1(+) bone marrow stem cells (SC), transferred to mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis, enhanced recovery, prevented relapses and promoted myelin repair. SC-treated mice showed elevated interferon-gamma production and induction of indoleamine 2,3-dioxygenase (IDO) in CD11c(+) dendritic cells (DC). IDO induction was specific since in the presence of IDO-producing CD11c(+) DC, PLP stimulated T cell proliferation was inhibited and the IDO-inhibitor, 1-MT, abrogated the SC effect...
January 2008: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/17594069/ido-expression-in-the-brain-a-double-edged-sword
#20
REVIEW
Erik Kwidzinski, Ingo Bechmann
The tryptophan-catabolizing enzyme indoleamine-2,3-dioxygenase (IDO) initiates the first and rate-limiting step of the kynurenine pathway. It is induced by proinflammatory cytokines such as interferon-beta and interferon-gamma and has established effects in the control of intracellular parasites. The recent detection of its decisive function in immune tolerance at the maternal-fetal interface stimulated various studies unraveling its regulatory effect on T cells in many pathologies. In the brain, IDO can be induced in microglia by interferon-gamma-producing T helper (Th) 1 cells, thereby initiating a negative feedback loop which downmodulates neuroinflammation in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS)...
December 2007: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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