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Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts

BACKGROUND: The kynurenine pathway (KP) is the main route of tryptophan degradation in the human body and generates several neuroactive and immunomodulatory metabolites. Altered levels of KP-metabolites have been observed in neuropsychiatric and neurodegenerative disorders as well as in patients wit...

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Autores principales: Asp, Linnéa, Johansson, Anne-Sofie, Mann, Amandeep, Owe-Larsson, Björn, Urbanska, Ewa M, Kocki, Tomasz, Kegel, Magdalena, Engberg, Göran, Lundkvist, Gabriella BS, Karlsson, Håkan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204223/
https://www.ncbi.nlm.nih.gov/pubmed/21982155
http://dx.doi.org/10.1186/1476-9255-8-25
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author Asp, Linnéa
Johansson, Anne-Sofie
Mann, Amandeep
Owe-Larsson, Björn
Urbanska, Ewa M
Kocki, Tomasz
Kegel, Magdalena
Engberg, Göran
Lundkvist, Gabriella BS
Karlsson, Håkan
author_facet Asp, Linnéa
Johansson, Anne-Sofie
Mann, Amandeep
Owe-Larsson, Björn
Urbanska, Ewa M
Kocki, Tomasz
Kegel, Magdalena
Engberg, Göran
Lundkvist, Gabriella BS
Karlsson, Håkan
author_sort Asp, Linnéa
collection PubMed
description BACKGROUND: The kynurenine pathway (KP) is the main route of tryptophan degradation in the human body and generates several neuroactive and immunomodulatory metabolites. Altered levels of KP-metabolites have been observed in neuropsychiatric and neurodegenerative disorders as well as in patients with affective disorders. The purpose of the present study was to investigate if skin derived human fibroblasts are useful for studies of expression of enzymes in the KP. METHODS: Fibroblast cultures were established from cutaneous biopsies taken from the arm of consenting volunteers. Such cultures were subsequently treated with interferon (IFN)-γ 200 U/ml and/or tumor necrosis factor (TNF)-α, 100 U/ml for 48 hours in serum-free medium. Levels of transcripts encoding different enzymes were determined by real-time PCR and levels of kynurenic acid (KYNA) were determined by HPLC. RESULTS: At base-line all cultures harbored detectable levels of transcripts encoding KP enzymes, albeit with considerable variation across individuals. Following cytokine treatment, considerable changes in many of the transcripts investigated were observed. For example, increases in the abundance of transcripts encoding indoleamine 2,3-dioxygenase, kynureninase or 3-hydroxyanthranilic acid oxygenase and decreases in the levels of transcripts encoding tryptophan 2,3-dioxygenase, kynurenine aminotransferases or quinolinic acid phosphoribosyltransferase were observed following IFN-γ and TNF-α treatment. Finally, the fibroblast cultures released detectable levels of KYNA in the cell culture medium at base-line conditions, which were increased after IFN-γ, but not TNF-α, treatments. CONCLUSIONS: All of the investigated genes encoding KP enzymes were expressed in human fibroblasts. Expression of many of these appeared to be regulated in response to cytokine treatment as previously reported for other cell types. Fibroblast cultures, thus, appear to be useful for studies of disease-related abnormalities in the kynurenine pathway of tryptophan degradation.
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spelling pubmed-32042232011-10-30 Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts Asp, Linnéa Johansson, Anne-Sofie Mann, Amandeep Owe-Larsson, Björn Urbanska, Ewa M Kocki, Tomasz Kegel, Magdalena Engberg, Göran Lundkvist, Gabriella BS Karlsson, Håkan J Inflamm (Lond) Research BACKGROUND: The kynurenine pathway (KP) is the main route of tryptophan degradation in the human body and generates several neuroactive and immunomodulatory metabolites. Altered levels of KP-metabolites have been observed in neuropsychiatric and neurodegenerative disorders as well as in patients with affective disorders. The purpose of the present study was to investigate if skin derived human fibroblasts are useful for studies of expression of enzymes in the KP. METHODS: Fibroblast cultures were established from cutaneous biopsies taken from the arm of consenting volunteers. Such cultures were subsequently treated with interferon (IFN)-γ 200 U/ml and/or tumor necrosis factor (TNF)-α, 100 U/ml for 48 hours in serum-free medium. Levels of transcripts encoding different enzymes were determined by real-time PCR and levels of kynurenic acid (KYNA) were determined by HPLC. RESULTS: At base-line all cultures harbored detectable levels of transcripts encoding KP enzymes, albeit with considerable variation across individuals. Following cytokine treatment, considerable changes in many of the transcripts investigated were observed. For example, increases in the abundance of transcripts encoding indoleamine 2,3-dioxygenase, kynureninase or 3-hydroxyanthranilic acid oxygenase and decreases in the levels of transcripts encoding tryptophan 2,3-dioxygenase, kynurenine aminotransferases or quinolinic acid phosphoribosyltransferase were observed following IFN-γ and TNF-α treatment. Finally, the fibroblast cultures released detectable levels of KYNA in the cell culture medium at base-line conditions, which were increased after IFN-γ, but not TNF-α, treatments. CONCLUSIONS: All of the investigated genes encoding KP enzymes were expressed in human fibroblasts. Expression of many of these appeared to be regulated in response to cytokine treatment as previously reported for other cell types. Fibroblast cultures, thus, appear to be useful for studies of disease-related abnormalities in the kynurenine pathway of tryptophan degradation. BioMed Central 2011-10-08 /pmc/articles/PMC3204223/ /pubmed/21982155 http://dx.doi.org/10.1186/1476-9255-8-25 Text en Copyright ©2011 Asp et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Asp, Linnéa
Johansson, Anne-Sofie
Mann, Amandeep
Owe-Larsson, Björn
Urbanska, Ewa M
Kocki, Tomasz
Kegel, Magdalena
Engberg, Göran
Lundkvist, Gabriella BS
Karlsson, Håkan
Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts
title Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts
title_full Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts
title_fullStr Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts
title_full_unstemmed Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts
title_short Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts
title_sort effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204223/
https://www.ncbi.nlm.nih.gov/pubmed/21982155
http://dx.doi.org/10.1186/1476-9255-8-25
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