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Tryptophan Metabolism Along the Kynurenine Pathway Downstream of Toll-like Receptor Stimulation in Peripheral Monocytes
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
Prot Biomarkers Personalized Healthcare & Biomark, Innovat Med, Gothenburg, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
Prot Biomarkers Personalized Healthcare & Biomark, Innovat Med, Gothenburg, Sweden.;Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
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2016 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 84, no 5, 262-271 p.Article in journal (Refereed) Published
Abstract [en]

Tryptophan degradation along the kynurenine pathway is of central importance for the immune function. Toll-like receptors (TLRs), 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 TLRs 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.

Place, publisher, year, edition, pages
2016. Vol. 84, no 5, 262-271 p.
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Immunology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-308912DOI: 10.1111/sji.12479ISI: 000387049300002PubMedID: 27607184OAI: oai:DiVA.org:uu-308912DiVA: diva2:1051214
Funder
Swedish Society for Medical Research (SSMF), 2009-7053 2013-2838The Swedish Brain FoundationSwedish Society of MedicineTorsten Söderbergs stiftelseAstraZenecaThe Karolinska Institutet's Research Foundation
Available from: 2016-12-01 Created: 2016-12-01 Last updated: 2016-12-01Bibliographically approved

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