The interplay between cytokines and the Kynurenine pathway in inflammation and atherosclerosis

Baumgartner, Roland; Forteza, María J.; Ketelhuth, Daniel F.J.

doi:10.1016/j.cyto.2017.09.004

Cited by 105 publications

(103 citation statements)

References 139 publications

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“…However, our result contradicts those reports where the accumulation of KPMs such as 3-HK and 3HAA mediated cell apoptosis in T-B-and natural killer cells (NK) (25). Alternatively, Fallarino et al reported that 3HAA would induce selective apoptosis in Th1 but not Th2 cells (73).…”

Section: Discussioncontrasting

confidence: 99%

“…3HAA is known to be particularly unstable over time and sensitive to light (20,24). It has been reported that accumulation of KYN induces T-Band natural killer (NK)-cells apoptosis (25). The concentration of different metabolites in the KP is controlled by groups of enzymes such as IDO1, IDO2, and tryptophan 2, 3-dioxygenase (TDO2), three rate-limiting enzymes that catalyze the cleavage of TRP into KYN (26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

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Immunometabolic Network Interactions of the Kynurenine Pathway in Cutaneous Malignant Melanoma

et al. 2020

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Dysregulation of the kynurenine pathway has been regarded as a mechanism of tumor immune escape by the enzymatic activity of indoleamine 2, 3 dioxygenase and kynurenine production. However, the immune-modulatory properties of other kynurenine metabolites such as kynurenic acid, 3-hydroxykynurenine, and anthranilic acid are poorly understood. In this study, plasma from patients diagnosed with metastatic cutaneous malignant melanoma (CMM) was obtained before (PRE) and during treatment (TRM) with inhibitors of mitogen-activated protein kinase pathway (MAPKIs). Immuno-oncology related protein profile and kynurenine metabolites were analyzed by proximity extension assay (PEA) and LC/MS-MS, respectively. Correlation network analyses of the data derived from PEA and LC/MS-MS identified a set of proteins that modulate the differentiation of Th1 cells, which is linked to 3-hydroxykynurenine levels. Moreover, MAPKIs treatments are associated with alteration of 3-hydroxykynurenine and 3hydroxyanthranilic acid (3HAA) concentrations and led to higher "CXCL11," and "KLRD1" expression that are involved in T and NK cells activation. These findings imply that the kynurenine pathway is pathologically relevant in patients with CMM.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunometabolic Network Interactions of the Kynurenine Pathway in Cutaneous Malignant Melanoma

et al. 2020

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“…11 Ido1 induction may lead to focal depletion of Trp at the site of inflammation or infection, which can directly limit viral replication . The intracellular Kyn generated by Ido1 is either released or metabolized into downstream “kynurenines” (kynurenic acid [KynA] or quinolinic acid [QuinA]), which have both neuro‐ and immunomodulatory consequences . Extracellular KynA serves as an N ‐methyl‐ d ‐aspartate (NMDA) receptor antagonist and is considered neuroprotective.…”

Section: Introductionmentioning

confidence: 99%

“…11 The intracellular Kyn generated by Ido1 is either released or metabolized into downstream "kynurenines" (kynurenic acid [KynA] or quinolinic acid [QuinA]), which have both neuro-and immunomodulatory consequences. 12,13 Extracellular KynA serves as an N-methyl-Daspartate (NMDA) receptor antagonist and is considered neuroprotective. Conversely, QuinA is a glutamatergic NMDA receptor agonist and can evoke neurotoxic and ictogenic responses.…”

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confidence: 99%

Indoleamine 2,3‐dioxygenase 1 deletion promotes Theiler's virus–induced seizures in C57BL/6J mice

et al. 2019

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Summary Objective Viral encephalitis increases the risk for developing seizures and epilepsy. Indoleamine 2,3‐dioxygenase 1 (Ido1) is induced by inflammatory cytokines and functions to metabolize tryptophan to kynurenine. Kynurenine can be further metabolized to produce kynurenic acid and the N‐methyl‐d‐aspartate receptor agonist quinolinic acid (QuinA). In the present study, we sought to determine the role of Ido1 in promoting seizures in an animal model of viral encephalitis. Methods C57BL/6J and Ido1 knockout mice (Ido1‐KO) were infected with Theiler's murine encephalomyelitis virus (TMEV). Quantitative real‐time polymerase chain reaction was used to evaluate hippocampal expression of proinflammatory cytokines, Ido1, and viral RNA. Body weights and seizure scores were recorded daily. Elevated zero maze was used to assess differences in behavior, and hippocampal pathology was determined by immunohistochemistry. Results Infected C57BL/6J mice up‐regulated proinflammatory cytokines, Ido1, and genes encoding the enzymatic cascade responsible for QuinA production in the kynurenine pathway prior to the onset of seizures. Seizure incidence was elevated in Ido1‐KO compared to C57BL/6J mice. Infection increased locomotor activity in Ido1‐KO compared to C57BL/6J mice. Furthermore, the occurrence of seizures was associated with hyperexcitability. Neither expression of proinflammatory cytokines nor viral RNA was altered as a result of genotype. Immunohistochemical analysis revealed increased hippocampal pathology in Ido1‐KO mice. Significance Our findings suggest that Ido1 deletion promotes seizures and neuropathogenesis during acute TMEV encephalitis.

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“…However, they consistently observed vasodilation using a mixture of tryptophan and either the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) or singlet oxygen, a reactive oxygen species that is generated by IDO1. The expression of IDO1 is normally low in cell types other than immune cells, but can be upregulated by inflammatory proteins known as cytokines and by redox stress 3,4 -which means that IDO1 is often expressed in the presence of oxidants.…”

Section: Dav I D a K A S Smentioning

confidence: 99%

Fresh evidence overturns the identification of a factor involved in blood-vessel dilation

Kass¹

2019

Nature

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The interplay between cytokines and the Kynurenine pathway in inflammation and atherosclerosis

Cited by 105 publications

References 139 publications

Immunometabolic Network Interactions of the Kynurenine Pathway in Cutaneous Malignant Melanoma

Immunometabolic Network Interactions of the Kynurenine Pathway in Cutaneous Malignant Melanoma

Indoleamine 2,3‐dioxygenase 1 deletion promotes Theiler's virus–induced seizures in C57BL/6J mice

Fresh evidence overturns the identification of a factor involved in blood-vessel dilation

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