| Influence of immunosuppressive agents on tryptophan degradation and neopterin production in human peripheral blood mononuclear cells. | |
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MedLine Citation:
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PMID: 21742032 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The anti-proliferative and immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) degrades the essential amino acid tryptophan via the kynurenine pathway. IDO is stimulated during cellular immune responses preferentially by Th1-type cytokine interferon-γ (IFN-γ). IDO activity is estimated by calculating the kynurenine to tryptophan ratio (Kyn/Trp). In human monocyte-derived macrophages and dendritic cells, GTP-cyclohydrolase I is induced in parallel to IDO and produces neopterin. This study investigated the effects of common immunosuppressants on freshly isolated human peripheral blood mononuclear cells (PBMC) in vitro. PBMC were incubated with compounds for 30min and then either left unstimulated or stimulated with mitogen phytohaemagglutinin (PHA). Concentrations of tryptophan, kynurenine and neopterin were measured in supernatants after 48h. Kyn/Trp, neopterin and IFN-γ concentrations were significantly higher in PHA-stimulated vs. unstimulated PBMC. Tacrolimus (FK506), cyclosporine A (CsA), sirolimus and methylprednisolone dose-dependently inhibited tryptophan degradation and neopterin production. FK506, CsA and sirolimus showed significant inhibition at concentrations as low as 0.1μg/ml, whereas prednisolone and methylprednisolone required higher doses to suppress tryptophan degradation. Mycophenolate-mofetil suppressed neopterin formation more efficiently than Kyn/Trp. All tested drugs also strongly decreased mitogen-induced IFN-γ concentrations. Overall the investigated immunosuppressants are effective to inhibit IDO activity and neopterin production in a similar and dose-dependent manner, however with some differences in IC50s when comparing individual compounds. The corresponding changes of IFN-γ concentrations are in line with its role as a trigger of both biochemical changes. |
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Authors:
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Sebastian Schroecksnadel; Robert Sucher; Katharina Kurz; Dietmar Fuchs; Gerald Brandacher |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-1 |
Journal Detail:
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Title: Transplant immunology Volume: - ISSN: 1878-5492 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9309923 Medline TA: Transpl Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier B.V. |
Affiliation:
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Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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