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Title: LPS-induced NF-{kappa}B expression in THP-1Blue cells correlates with neopterin production and activity of indoleamine 2,3-dioxygenase

Abstract

Research highlights: {yields} LPS induces NF-{kappa}B, neopterin formation and tryptophan degradation in THP-1 cells. {yields} Close dose- and time-dependent correlations exist between these biochemical events. {yields} Data provides some evidence for a parallel induction of them upon TLR stimulation. {yields} Results can be of considerable relevance also in vivo. -- Abstract: Neopterin production is induced in human monocyte-derived macrophages and dendritic cells upon stimulation with Th1-type cytokine interferon-{gamma} (IFN-{gamma}). In parallel, IFN-{gamma} induces the tryptophan-(trp)-degrading enzyme indoleamine 2,3-dioxygenase (IDO) and triggers the formation of reactive oxygen species (ROS). Translocation of the signal transduction element nuclear factor-{kappa}B (NF-{kappa}B) is induced by ROS and accelerates the pro-inflammatory response by activation of other pro-inflammatory pathways. Therefore, a close relationship between NF-{kappa}B expression, the production of neopterin and the degradation of trp can be assumed, although this has not been demonstrated so far. In the present in vitro study we compared the influence of lipopolysaccharide (LPS) on NF-{kappa}B activation, neopterin formation and the degradation of trp in THP-1Blue cells, which represent the human myelomonocytic cell line THP-1 stably transfected with an NF-{kappa}B inducible reporter system. In cells stimulated with LPS, a significant induction of NF-{kappa}B was observed, and this was paralleled by an increasemore » of kynureunine (kyn) and neopterin concentrations and a decline of trp. The increase of the kyn to trp quotient indicates accelerated IDO activity. Higher LPS concentrations and longer incubation of cells were associated with higher activities of all three biochemical pathways and significant correlations existed between NF-{kappa}B activation, neopterin release and trp degradation (all p < 0.001). We conclude that there is a parallel induction of NF-{kappa}B, neopterin formation and trp degradation in monocytic THP-1 cells, which is elicited by pro-inflammatory triggers like LPS during innate immune responses.« less

Authors:
 [1];  [1];  [2];  [3];  [2];  [3];  [1]
  1. Division of Biological Chemistry, Innsbruck Medical University, Innsbruck (Austria)
  2. Department of Internal Medicine, Innsbruck Medical University, Innsbruck (Austria)
  3. Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck (Austria)
Publication Date:
OSTI Identifier:
22202761
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 399; Journal Issue: 4; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; DENDRITES; DOSES; ENZYMES; IN VITRO; IN VIVO; INFLAMMATION; INTERFERON; MACROPHAGES; MONOCYTES; STIMULATION; TRANSLOCATION; TRYPTOPHAN

Citation Formats

Schroecksnadel, Sebastian, Jenny, Marcel, Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck, Kurz, Katharina, Klein, Angela, Ledochowski, Maximilian, Uberall, Florian, and Fuchs, Dietmar. LPS-induced NF-{kappa}B expression in THP-1Blue cells correlates with neopterin production and activity of indoleamine 2,3-dioxygenase. United States: N. p., 2010. Web. doi:10.1016/J.BBRC.2010.07.134.
Schroecksnadel, Sebastian, Jenny, Marcel, Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck, Kurz, Katharina, Klein, Angela, Ledochowski, Maximilian, Uberall, Florian, & Fuchs, Dietmar. LPS-induced NF-{kappa}B expression in THP-1Blue cells correlates with neopterin production and activity of indoleamine 2,3-dioxygenase. United States. https://doi.org/10.1016/J.BBRC.2010.07.134
Schroecksnadel, Sebastian, Jenny, Marcel, Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck, Kurz, Katharina, Klein, Angela, Ledochowski, Maximilian, Uberall, Florian, and Fuchs, Dietmar. 2010. "LPS-induced NF-{kappa}B expression in THP-1Blue cells correlates with neopterin production and activity of indoleamine 2,3-dioxygenase". United States. https://doi.org/10.1016/J.BBRC.2010.07.134.
@article{osti_22202761,
title = {LPS-induced NF-{kappa}B expression in THP-1Blue cells correlates with neopterin production and activity of indoleamine 2,3-dioxygenase},
author = {Schroecksnadel, Sebastian and Jenny, Marcel and Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck and Kurz, Katharina and Klein, Angela and Ledochowski, Maximilian and Uberall, Florian and Fuchs, Dietmar},
abstractNote = {Research highlights: {yields} LPS induces NF-{kappa}B, neopterin formation and tryptophan degradation in THP-1 cells. {yields} Close dose- and time-dependent correlations exist between these biochemical events. {yields} Data provides some evidence for a parallel induction of them upon TLR stimulation. {yields} Results can be of considerable relevance also in vivo. -- Abstract: Neopterin production is induced in human monocyte-derived macrophages and dendritic cells upon stimulation with Th1-type cytokine interferon-{gamma} (IFN-{gamma}). In parallel, IFN-{gamma} induces the tryptophan-(trp)-degrading enzyme indoleamine 2,3-dioxygenase (IDO) and triggers the formation of reactive oxygen species (ROS). Translocation of the signal transduction element nuclear factor-{kappa}B (NF-{kappa}B) is induced by ROS and accelerates the pro-inflammatory response by activation of other pro-inflammatory pathways. Therefore, a close relationship between NF-{kappa}B expression, the production of neopterin and the degradation of trp can be assumed, although this has not been demonstrated so far. In the present in vitro study we compared the influence of lipopolysaccharide (LPS) on NF-{kappa}B activation, neopterin formation and the degradation of trp in THP-1Blue cells, which represent the human myelomonocytic cell line THP-1 stably transfected with an NF-{kappa}B inducible reporter system. In cells stimulated with LPS, a significant induction of NF-{kappa}B was observed, and this was paralleled by an increase of kynureunine (kyn) and neopterin concentrations and a decline of trp. The increase of the kyn to trp quotient indicates accelerated IDO activity. Higher LPS concentrations and longer incubation of cells were associated with higher activities of all three biochemical pathways and significant correlations existed between NF-{kappa}B activation, neopterin release and trp degradation (all p < 0.001). We conclude that there is a parallel induction of NF-{kappa}B, neopterin formation and trp degradation in monocytic THP-1 cells, which is elicited by pro-inflammatory triggers like LPS during innate immune responses.},
doi = {10.1016/J.BBRC.2010.07.134},
url = {https://www.osti.gov/biblio/22202761}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 399,
place = {United States},
year = {Fri Sep 03 00:00:00 EDT 2010},
month = {Fri Sep 03 00:00:00 EDT 2010}
}