Tryptophan Metabolism Along the Kynurenine Pathway Downstream of Toll‐like Receptor Stimulation in Peripheral Monocytes
Open accessAbstract
Tryptophan degradation along the kynurenine pathway is of central importance for the immune function. Toll‐like receptors ( TLR s), representing the first line of immune defence against pathogens, are expressed in various cell types. The most abundant expression is found on monocytes, macrophages and dendritic cells. The aim of this study was to investigate whether stimulation with different TLR ligands induces the kynurenine pathway in human peripheral monocytes. Cell supernatants were analysed using a liquid chromatography/mass spectrometry to measure kynurenine, kynurenic acid ( KYNA ), quinolinic acid ( QUIN ) and tryptophan. Stimulation of TLR ‐2, TLR ‐3, TLR ‐4, TLR ‐7/8 and TLR ‐9 was found to induce the production of kynurenine, but only stimulation of TLR ‐3 increased levels of further downstream metabolites, such as KYNA and QUIN . Stimulation of TLR ‐1, TLR ‐5 and TLR ‐6 did not induce the kynurenine pathway. Taken together, this study provides novel evidence demonstrating that TLR activation induces a pattern of downstream tryptophan degradation along the kynurenine pathway in monocytes. The results of this study may implicate that TLR s can be used as new drug targets for the regulation of aberrant tryptophan metabolism along this pathway, a potential therapeutic strategy that may be of importance in several disorders.
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Activation of Toll-like receptor 3 in peripheral monocytes facilitates production of quinolinic acid.
“Activation of Toll-like receptor 3 (TLR3) in peripheral monocytes facilitates production of the metabolite quinolinic acid185”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [185]
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- Authors
- Orhan, F., Bhat, M., Sandberg, K., Ståhl, S., Piehl, F., Karolinska Schizophrenia Project (KaSP) consortium, Svensson, C., Erhardt, S., & Schwieler, L.
- Affiliations
- Karolinska Institutet (SE)
- Protein Biomarkers, Personalized Healthcare & Biomarker Laboratories Innovative Medicines Gothenburg Sweden
- Uppsala University (SE)
- Corresponding author
- Schwieler, L.
- Venue
- Scandinavian Journal of Immunology
- Publisher
- Wiley
- Published
- 2016-10-26
- Volume
- 84
- Issue
- 5
- Pages
- 262-271
- ISSN
- 0300-9475 (ISSN-L)
- 1365-3083
- OpenAlex
- W2511451630
- Cited by
- 47
- References
- 59
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 11 · 2022: 5 · 2021: 5 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 3
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Scandinavian Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medicinska Forskningsrådet (2009‐7053, 2013‐2838)
- Hjärnfonden
- Svenska Läkaresällskapet
- Torsten Söderbergs Stiftelse
- Karolinska Institutet
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- tryptophan metabolism, kynurenine pathway, Toll-like receptors, peripheral blood monocytes, TLR3, kynurenic acid, quinolinic acid, TLR ligands, tryptophan degradation, therapeutic target
- MeSH terms
- Flagellin, Gene Expression Regulation, Humans, Hydrolysis, Imidazoles, Kynurenic Acid, Kynurenine, Lipopolysaccharides, Listeria monocytogenes, Monocytes, Poly I-C, Tryptophan, Signal Transduction, Quinolinic Acid, Protein Isoforms, Toll-Like Receptors, Lipopeptides, Primary Cell Culture
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