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Expression of the Kynurenine Pathway in Human Peripheral Blood Mononuclear Cells: Implications for Inflammatory and Neurodegenerative Disease
by
Jones, Simon P.
, de Bie, Josien
, Brew, Bruce J.
, Franco, Nunzio F.
, Guillemin, Gilles J.
, Lim, Chai K.
, Varney, Bianca
, Brown, David A.
, Sundaram, Gayathri
in
Activation
/ Biological response modifiers
/ Cytokines
/ Cytometry
/ Dementia
/ Disease
/ Enzymes
/ Female
/ Flow cytometry
/ Free radicals
/ Gas chromatography
/ Gene expression
/ Gene Expression Regulation, Enzymologic
/ Health sciences
/ High performance liquid chromatography
/ Humans
/ Immune response
/ Immune system
/ Immunological tolerance
/ Immunosuppression
/ Indoleamine-Pyrrole 2,3,-Dioxygenase - biosynthesis
/ Inflammatory diseases
/ Interferon
/ Kynurenine - metabolism
/ Kynurenine 3-Monooxygenase - biosynthesis
/ Leukocytes (mononuclear)
/ Leukocytes, Mononuclear - metabolism
/ Leukocytes, Mononuclear - pathology
/ Ligands
/ Liquid chromatography
/ Lymphocytes
/ Male
/ Mass spectrometry
/ Mass spectroscopy
/ Medical research
/ Medicine
/ Metabolism
/ Metabolites
/ Monocytes
/ Neopterin
/ Nervous system diseases
/ Neurodegenerative Diseases - metabolism
/ Neurodegenerative Diseases - pathology
/ Neurosciences
/ Neurotoxicity
/ Pathogenesis
/ Peripheral blood mononuclear cells
/ Phosphoribosyltransferase
/ Quinolinate phosphoribosyltransferase
/ Quinolinic acid
/ Rodents
/ Tryptophan
/ Tryptophan 2,3-dioxygenase
/ Up-Regulation
2015
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Expression of the Kynurenine Pathway in Human Peripheral Blood Mononuclear Cells: Implications for Inflammatory and Neurodegenerative Disease
by
Jones, Simon P.
, de Bie, Josien
, Brew, Bruce J.
, Franco, Nunzio F.
, Guillemin, Gilles J.
, Lim, Chai K.
, Varney, Bianca
, Brown, David A.
, Sundaram, Gayathri
in
Activation
/ Biological response modifiers
/ Cytokines
/ Cytometry
/ Dementia
/ Disease
/ Enzymes
/ Female
/ Flow cytometry
/ Free radicals
/ Gas chromatography
/ Gene expression
/ Gene Expression Regulation, Enzymologic
/ Health sciences
/ High performance liquid chromatography
/ Humans
/ Immune response
/ Immune system
/ Immunological tolerance
/ Immunosuppression
/ Indoleamine-Pyrrole 2,3,-Dioxygenase - biosynthesis
/ Inflammatory diseases
/ Interferon
/ Kynurenine - metabolism
/ Kynurenine 3-Monooxygenase - biosynthesis
/ Leukocytes (mononuclear)
/ Leukocytes, Mononuclear - metabolism
/ Leukocytes, Mononuclear - pathology
/ Ligands
/ Liquid chromatography
/ Lymphocytes
/ Male
/ Mass spectrometry
/ Mass spectroscopy
/ Medical research
/ Medicine
/ Metabolism
/ Metabolites
/ Monocytes
/ Neopterin
/ Nervous system diseases
/ Neurodegenerative Diseases - metabolism
/ Neurodegenerative Diseases - pathology
/ Neurosciences
/ Neurotoxicity
/ Pathogenesis
/ Peripheral blood mononuclear cells
/ Phosphoribosyltransferase
/ Quinolinate phosphoribosyltransferase
/ Quinolinic acid
/ Rodents
/ Tryptophan
/ Tryptophan 2,3-dioxygenase
/ Up-Regulation
2015
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Expression of the Kynurenine Pathway in Human Peripheral Blood Mononuclear Cells: Implications for Inflammatory and Neurodegenerative Disease
by
Jones, Simon P.
, de Bie, Josien
, Brew, Bruce J.
, Franco, Nunzio F.
, Guillemin, Gilles J.
, Lim, Chai K.
, Varney, Bianca
, Brown, David A.
, Sundaram, Gayathri
in
Activation
/ Biological response modifiers
/ Cytokines
/ Cytometry
/ Dementia
/ Disease
/ Enzymes
/ Female
/ Flow cytometry
/ Free radicals
/ Gas chromatography
/ Gene expression
/ Gene Expression Regulation, Enzymologic
/ Health sciences
/ High performance liquid chromatography
/ Humans
/ Immune response
/ Immune system
/ Immunological tolerance
/ Immunosuppression
/ Indoleamine-Pyrrole 2,3,-Dioxygenase - biosynthesis
/ Inflammatory diseases
/ Interferon
/ Kynurenine - metabolism
/ Kynurenine 3-Monooxygenase - biosynthesis
/ Leukocytes (mononuclear)
/ Leukocytes, Mononuclear - metabolism
/ Leukocytes, Mononuclear - pathology
/ Ligands
/ Liquid chromatography
/ Lymphocytes
/ Male
/ Mass spectrometry
/ Mass spectroscopy
/ Medical research
/ Medicine
/ Metabolism
/ Metabolites
/ Monocytes
/ Neopterin
/ Nervous system diseases
/ Neurodegenerative Diseases - metabolism
/ Neurodegenerative Diseases - pathology
/ Neurosciences
/ Neurotoxicity
/ Pathogenesis
/ Peripheral blood mononuclear cells
/ Phosphoribosyltransferase
/ Quinolinate phosphoribosyltransferase
/ Quinolinic acid
/ Rodents
/ Tryptophan
/ Tryptophan 2,3-dioxygenase
/ Up-Regulation
2015
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Expression of the Kynurenine Pathway in Human Peripheral Blood Mononuclear Cells: Implications for Inflammatory and Neurodegenerative Disease
Journal Article
Expression of the Kynurenine Pathway in Human Peripheral Blood Mononuclear Cells: Implications for Inflammatory and Neurodegenerative Disease
2015
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Overview
The kynurenine pathway is a fundamental mechanism of immunosuppression and peripheral tolerance. It is increasingly recognized as playing a major role in the pathogenesis of a wide variety of inflammatory, neurodegenerative and malignant disorders. However, the temporal dynamics of kynurenine pathway activation and metabolite production in human immune cells is currently unknown. Here we report the novel use of flow cytometry, combined with ultra high-performance liquid chromatography and gas chromatography-mass spectrometry, to sensitively quantify the intracellular expression of three key kynurenine pathway enzymes and the main kynurenine pathway metabolites in a time-course study. This is the first study to show that up-regulation of indoleamine 2,3-dioxygenase (IDO-1), kynurenine 3-monoxygenase (KMO) and quinolinate phosphoribosyltransferase (QPRT) is lacking in lymphocytes treated with interferon gamma. In contrast, peripheral monocytes showed a significant elevation of kynurenine pathway enzymes and metabolites when treated with interferon gamma. Expression of IDO-1, KMO and QPRT correlated significantly with activation of the kynurenine pathway (kynurenine:tryptophan ratio), quinolinic acid concentration and production of the monocyte derived, pro-inflammatory immune response marker: neopterin. Our results also describe an original and sensitive methodological approach to quantify kynurenine pathway enzyme expression in cells. This has revealed further insights into the potential role of these enzymes in disease processes.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Biological response modifiers
/ Dementia
/ Disease
/ Enzymes
/ Female
/ Gene Expression Regulation, Enzymologic
/ High performance liquid chromatography
/ Humans
/ Indoleamine-Pyrrole 2,3,-Dioxygenase - biosynthesis
/ Kynurenine 3-Monooxygenase - biosynthesis
/ Leukocytes, Mononuclear - metabolism
/ Leukocytes, Mononuclear - pathology
/ Ligands
/ Male
/ Medicine
/ Neurodegenerative Diseases - metabolism
/ Neurodegenerative Diseases - pathology
/ Peripheral blood mononuclear cells
/ Quinolinate phosphoribosyltransferase
/ Rodents
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