Search results for "Kynurenine"

Regulation of kynurenine biosynthesis during influenza virus infection.

2017

Influenza A viruses (IAVs) remain serious threats to public health because of the shortage of effective means of control. Developing more effective virus control modalities requires better understanding of virus–host interactions. It has previously been shown that IAV induces the production of kynurenine, which suppresses T-cell responses, enhances pain hypersensitivity and disturbs behaviour in infected animals. However, the regulation of kynurenine biosynthesis during IAV infection remains elusive. Here we showed that IAV infection induced expression of interferons (IFNs), which upregulated production of indoleamine-2,3-dioxygenase (IDO1), which catalysed the kynurenine biosynthesis. Furt…

Metabolomics of the tryptophan-kynurenine degradation pathway and risk of atrial fibrillation and heart failure: potential modification effect of Med…

2021

BACKGROUND: The tryptophan–kynurenine pathway is linked to inflammation. We hypothesize that metabolites implicated in this pathway may be associated with the risk of heart failure (HF) or atrial fibrillation (AF) in a population at high risk of cardiovascular disease. OBJECTIVES: We aimed to prospectively analyze the associations of kynurenine-related metabolites with the risk of HF and AF and to analyze a potential effect modification by the randomized interventions of the PREDIMED (Prevención con Dieta Mediterránea) trial with Mediterranean diet (MedDiet). METHODS: Two case–control studies nested within the PREDIMED trial were designed. We selected 324 incident HF cases and 502 incident …

2021

The CMS4 mesenchymal subtype of colorectal cancer (CRC) is associated with poor prognosis and resistance to treatment. The cellular prion protein PrPC is overexpressed in CMS4 tumors and controls the expression of a panel of CMS4-specific genes in CRC cell lines. Here, we sought to investigate PrPC downstream pathways that may underlie its role in CMS4 CRC. By combining gene set enrichment analyses and gain and loss of function approaches in CRC cell lines, we identify the integrin-linked kinase ILK as a proximal effector of PrPC that mediates its control on the CMS4 phenotype. We further leveraged three independent large CRC cohorts to assess correlations in gene expression pattern with pa…

Exercise Diminishes Plasma Neurofilament Light Chain and Reroutes the Kynurenine Pathway in Multiple Sclerosis

2020

ObjectiveTo examine acute (single-bout) and training effects of high-intensity interval training (HIIT) vs standard exercise therapy (moderate continuous training [MCT]) on plasma neurofilament light chain (pNfL) and kynurenine (KYN) pathway of tryptophan degradation metabolites in persons with multiple sclerosis (pwMS).MethodsSixty-nine pwMS (Expanded Disability Status Scale score 3.0–6.0) were randomly assigned to a HIIT or an MCT group. Changes in pNfL and KYN pathway metabolites measured in blood plasma were assessed before, after, and 3 hours after the first training session as well as after the 3-week training intervention.ResultsAcute exercise reduced pNfL and increased the KYN pathw…

Kynurenine and Neopterin in Chronic Glomerulonephritis

1999

The results of our clinical observations of 102 patients with chronic glomerulonephritis with normal renal function have shown that hyperkynureninemia in 22,5% of patients develops in cases of pyridoxal-5-phosphate deficiency (hyperkynureninemia after peroral L-tryptophan load), but in 14,8% of patients through the stimulation of the cellular immune system (hyperkynureninemia at fasting state, increase of serum neopterin concentration). In all 20 patients with chronic renal failure hyperkynureninemia develops due to decreased renal function (increased serum kynurenine, neopterin and creatinine concentrations). Therefore, L-tryptophan peroral loading test with the determination of serum conc…

A fundamental catalytic difference between zinc and manganese dependent enzymes revealed in a bacterial isatin hydrolase

2018

Scientific reports 8(1), 13104 (2018). doi:10.1038/s41598-018-31259-y

Mast cells' involvement in inflammation pathways linked to depression: evidence in mastocytosis

2016

International audience; Converging sources of evidence point to a role for inflammation in the development of depression, fatigue and cognitive dysfunction. More precisely, the tryptophan (TRP) catabolism is thought to play a major role in inflammation-induced depression. Mastocytosis is a rare disease in which chronic symptoms, including depression, are related to mast cell accumulation and activation. Our objectives were to study the correlations between neuropsychiatric features and the TRP catabolism pathway in mastocytosis in order to demonstrate mast cells' potential involvement in inflammation-induced depression. Fifty-four patients with mastocytosis and a mean age of 50.1 years were…

Increases in Plasma Tryptophan Are Inversely Associated with Incident Cardiovascular Disease in the Prevención con Dieta Mediterránea (PREDIMED) Stud…

2017

Background: During development of cardiovascular disease (CVD), interferon-γ-mediated inflammation accelerates degradation of tryptophan into downstream metabolites. A Mediterranean diet (MedDiet) consisting of a high intake of extra-virgin olive oil (EVOO), nuts, fruits, vegetables, and cereals has been demonstrated to lower the risk of CVD. The longitudinal relation between tryptophan and its downstream metabolites and CVD in the context of a MedDiet is unstudied.Objective: We sought to investigate the relation between metabolites in the tryptophan-kynurenine pathway and CVD in the context of a MedDiet pattern.Methods: We used a case-cohort design nested in the Prevención con Dieta Medite…

Association of Tryptophan Metabolites with Incident Type 2 Diabetes in the PREDIMED Trial: A Case–Cohort Study

2018

Abstract BACKGROUND Metabolites of the tryptophan–kynurenine pathway (i.e., tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxyanthranilic) may be associated with diabetes development. Using a case–cohort design nested in the Prevención con Dieta Mediterránea (PREDIMED) study, we studied the associations of baseline and 1-year changes of these metabolites with incident type 2 diabetes (T2D). METHODS Plasma metabolite concentrations were quantified via LC-MS for n = 641 in a randomly selected subcohort and 251 incident cases diagnosed during 3.8 years of median follow-up. Weighted Cox models adjusted for age, sex, body mass index, and other T2D risk factors were used. RESULTS …

Decreased kynurenine pathway potentiate resilience to social defeat effect on cocaine rewa

2021

The kynurenine (KYN) pathway of tryptophan (TRP) degradation is activated by stress and inflammatory factors. It is now well established that social stress induces the activation of the immune system, with central inflammation and KYN metabolism being two of the main factors linking stress with depression. The aim of the present study was to evaluate the long-lasting changes in the KYN pathway induced by social defeat (SD) associated with the resilience or susceptibility to an increase in the conditioned rewarding effects of cocaine. Mice were exposed to repeated SD and 3 weeks later, a conditioned place preference (CPP) induced by a subthreshold dose of cocaine (1.5 mg/kg) was developed. K…