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LPS-induced NF-kappaB expression in THP-1Blue cells correlates with neopterin production and activity of indoleamine 2,3-dioxygenase.
Biochem Biophys Res Commun. 2010 Sep 03; 399(4):642-6.BB

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-kappaB (NF-kappaB) is induced by ROS and accelerates the pro-inflammatory response by activation of other pro-inflammatory pathways. Therefore, a close relationship between NF-kappaB 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-kappaB 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-kappaB inducible reporter system. In cells stimulated with LPS, a significant induction of NF-kappaB 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-kappaB activation, neopterin release and trp degradation (all p<0.001). We conclude that there is a parallel induction of NF-kappaB, neopterin formation and trp degradation in monocytic THP-1 cells, which is elicited by pro-inflammatory triggers like LPS during innate immune responses.

Authors+Show Affiliations

Division of Biological Chemistry, Innsbruck Medical University, Innsbruck, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20691158

Citation

Schroecksnadel, Sebastian, et al. "LPS-induced NF-kappaB Expression in THP-1Blue Cells Correlates With Neopterin Production and Activity of Indoleamine 2,3-dioxygenase." Biochemical and Biophysical Research Communications, vol. 399, no. 4, 2010, pp. 642-6.
Schroecksnadel S, Jenny M, Kurz K, et al. LPS-induced NF-kappaB expression in THP-1Blue cells correlates with neopterin production and activity of indoleamine 2,3-dioxygenase. Biochem Biophys Res Commun. 2010;399(4):642-6.
Schroecksnadel, S., Jenny, M., Kurz, K., Klein, A., Ledochowski, M., Uberall, F., & Fuchs, D. (2010). LPS-induced NF-kappaB expression in THP-1Blue cells correlates with neopterin production and activity of indoleamine 2,3-dioxygenase. Biochemical and Biophysical Research Communications, 399(4), 642-6. https://doi.org/10.1016/j.bbrc.2010.07.134
Schroecksnadel S, et al. LPS-induced NF-kappaB Expression in THP-1Blue Cells Correlates With Neopterin Production and Activity of Indoleamine 2,3-dioxygenase. Biochem Biophys Res Commun. 2010 Sep 3;399(4):642-6. PubMed PMID: 20691158.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - LPS-induced NF-kappaB expression in THP-1Blue cells correlates with neopterin production and activity of indoleamine 2,3-dioxygenase. AU - Schroecksnadel,Sebastian, AU - Jenny,Marcel, AU - Kurz,Katharina, AU - Klein,Angela, AU - Ledochowski,Maximilian, AU - Uberall,Florian, AU - Fuchs,Dietmar, Y1 - 2010/08/04/ PY - 2010/07/29/received PY - 2010/07/30/accepted PY - 2010/8/10/entrez PY - 2010/8/10/pubmed PY - 2010/10/12/medline SP - 642 EP - 6 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 399 IS - 4 N2 - 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-kappaB (NF-kappaB) is induced by ROS and accelerates the pro-inflammatory response by activation of other pro-inflammatory pathways. Therefore, a close relationship between NF-kappaB 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-kappaB 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-kappaB inducible reporter system. In cells stimulated with LPS, a significant induction of NF-kappaB 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-kappaB activation, neopterin release and trp degradation (all p<0.001). We conclude that there is a parallel induction of NF-kappaB, neopterin formation and trp degradation in monocytic THP-1 cells, which is elicited by pro-inflammatory triggers like LPS during innate immune responses. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/20691158/LPS_induced_NF_kappaB_expression_in_THP_1Blue_cells_correlates_with_neopterin_production_and_activity_of_indoleamine_23_dioxygenase_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(10)01467-1 DB - PRIME DP - Unbound Medicine ER -