Cited by 497Tryptophan and brain disordersNeuroinflammation and Neurodegeneration MechanismsAmino Acid Enzymes and Metabolism

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Expression of indoleamine 2,3-dioxygenase and production of quinolinic acid by human microglia, astrocytes, and neurons

Guillemin, Gilles J., Smythe, George, Takikawa, Osamu, Brew, Bruce J.·2005·Glia

DOI 10.1002/glia.20090

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Abstract

There is good evidence that the kynurenine pathway (KP) and one of its end products, quinolinic acid (QUIN) play a role in the pathogenesis of several major neurological diseases. While QUIN has been shown to be produced in neurotoxic concentrations by macrophages and microglia, the capacity of astrocytes and neurons to produce QUIN is controversial. Using interferon gamma (IFN‐γ)‐stimulated primary cultures of human mixed brain cells, we assayed expression of the KP regulatory enzyme indoleamine 2,3‐dioxygenase (IDO) and QUIN production by immunocytochemistry. Using IFN‐γ‐stimulated purified cultures of neurons, astrocytes, microglia and macrophages, we studied IDO expression by RT‐PCR and production of QUIN using mass spectrometry. We found that astrocytes, neurons, and microglia expressed IDO but only microglia were able to produce detectable amounts of QUIN. However, astrocytes and neurons had the ability to catabolize QUIN. This study also provides the first evidence of IDO expression and lack of production of QUIN in culture of primary human neurons. © 2004 Wiley‐Liss, Inc.

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Reliable chromatographic assay for measuring of indoleamine 2,3-dioxygenase 1 (IDO1) activity in human cancer cells
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“Matrix effect % ð Þ 1⁄4 Mean peak area in sample B Mean peak area in blank sample Mean peak area in sample C 100 (4) Recovery % ð Þ 1⁄4 Mean peak area in sample A Mean peak area in blank sample Mean peak area in sample B Mean peak area in blank sample 100 (3) JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY 585”
Background
Tat-indoleamine 2,3-dioxygenase 1 elicits neuroprotective effects on ischemic injury
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Distinct Patterns of Tryptophan Maintenance in Tissues during Kynurenine Pathway Activation in Simian Immunodeficiency Virus-Infected Macaques
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“The initial step involves conversion of TRP to KYN, catalyzed by enzymes tryptophan 2,3-dioxygenase (TDO) and enzyme indoleamine 2,3-dioxygenase (IDO) [15, 16].”
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“Consistent with established biology, astrocytes (via KATs) favour KYNA, a metabolite with established neuroprotective properties, whereas microglia (via KMO) are a predominant source of the neurotoxic QUIN [26–28].”

Authors: Guillemin, G. J., Smythe, G., Takikawa, O., & Brew, B. J.
Affiliations: UNSW Sydney (AU)
Hokkaido University (JP)
Corresponding author: Guillemin, Gilles J.
ORCID: Guillemin, Gilles J.
Brew, Bruce J.
Venue: Glia
Publisher: Wiley
Published: 2004-07-06
Volume: 49
Issue: 1
Pages: 15-23
ISSN: 0894-1491 (ISSN-L)
1098-1136
DOI: 10.1002/glia.20090
OpenAlex: W2042731928
Cited by: 497
References: 0
Citations by year: 2026: 17 · 2025: 15 · 2024: 27 · 2023: 15 · 2022: 30 · 2021: 29 · 2020: 40 · 2019: 23 · 2018: 26 · 2017: 25 · 2016: 36 · 2015: 19 · 2014: 30 · 2013: 30 · 2012: 19
FWCI: 5.62
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Glia (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords: indoleamine 2,3-dioxygenase, quinolinic acid, kynurenine pathway, microglia, astrocytes, neurons, interferon-gamma, neuroinflammation
MeSH terms: Astrocytes, Brain, Brain Chemistry, Cells, Cultured, Encephalitis, Humans, Immunohistochemistry, Interferon-gamma, Kynurenine, Macrophages, Neurons, Mass Spectrometry, Tryptophan Oxygenase, Molecular Structure, Signal Transduction, Quinolinic Acid, Microglia, Coculture Techniques, Indoleamine-Pyrrole 2,3,-Dioxygenase

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Expression of indoleamine 2,3-dioxygenase and production of quinolinic acid by human microglia, astrocytes, and neurons

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