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Immunomodulatory effects in vitro of vitamin K antagonist acenocoumarol.
Thromb Res. 2013 Jun; 131(6):e264-9.TR

Abstract

Neopterin production and tryptophan breakdown by indoleamine 2,3-dioxygenase (IDO) are induced within cell-mediated (=Th1-type) immune response, and in patients with coronary artery disease, serum neopterin and the kynurenine to tryptophan ratio (Kyn/Trp) are significantly predictive for cardiovascular and total mortality. To examine the potential impact of vitamin K-antagonist acenocoumarol (Sintrom) on the inflammatory response we investigated its effect on freshly isolated peripheral blood mononuclear cells (PBMC) from healthy donors, on myelomonocytic THP1-Blue and on intestinal Caco-2 cells in vitro. PBMC were incubated with increasing doses of acenocoumarol, and after 30 min either left unstimulated or stimulated with the mitogen phytohemagglutinin (PHA). Concentrations of neopterin, tryptophan, kynurenine, interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α) were measured in supernatants of PBMC after 48 h. Caco-2 cells were stimulated with IFN-γ and Kyn/Trp was used as readout. In THP1-Blue cells, the induction of NF-κB dependent reporter gene expression upon stimulation with lipopolysaccharide (LPS) was determined as an indicator of pro-inflammatory response. Upon stimulation, all measured immune response markers increased significantly compared to unstimulated cells. Acenocoumarol had no effect in unstimulated cells but in PHA-stimulated PBMC tryptophan breakdown and the formation of neopterin, as well as IFN-γ and TNF-α, were dose-dependently suppressed at concentrations as low as 10 μg/ml. Likewise, acenocoumarol dose-dependently inhibited tryptophan breakdown in IFN-γ stimulated Caco-2 cells. Interestingly, NF-κB expression was super-induced in the LPS treated cells. Data suggest that the immunomodulatory capacity of acenocoumarol contributes to its therapeutic efficacy.

Authors+Show Affiliations

Division of Biological Chemistry, 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

23481478

Citation

Schroecksnadel, S, et al. "Immunomodulatory Effects in Vitro of Vitamin K Antagonist Acenocoumarol." Thrombosis Research, vol. 131, no. 6, 2013, pp. e264-9.
Schroecksnadel S, Gostner J, Jenny M, et al. Immunomodulatory effects in vitro of vitamin K antagonist acenocoumarol. Thromb Res. 2013;131(6):e264-9.
Schroecksnadel, S., Gostner, J., Jenny, M., Kurz, K., Schennach, H., Weiss, G., & Fuchs, D. (2013). Immunomodulatory effects in vitro of vitamin K antagonist acenocoumarol. Thrombosis Research, 131(6), e264-9. https://doi.org/10.1016/j.thromres.2013.02.012
Schroecksnadel S, et al. Immunomodulatory Effects in Vitro of Vitamin K Antagonist Acenocoumarol. Thromb Res. 2013;131(6):e264-9. PubMed PMID: 23481478.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunomodulatory effects in vitro of vitamin K antagonist acenocoumarol. AU - Schroecksnadel,S, AU - Gostner,J, AU - Jenny,M, AU - Kurz,K, AU - Schennach,H, AU - Weiss,G, AU - Fuchs,D, Y1 - 2013/03/05/ PY - 2012/12/25/received PY - 2013/02/11/revised PY - 2013/02/14/accepted PY - 2013/3/14/entrez PY - 2013/3/14/pubmed PY - 2014/1/3/medline SP - e264 EP - 9 JF - Thrombosis research JO - Thromb. Res. VL - 131 IS - 6 N2 - Neopterin production and tryptophan breakdown by indoleamine 2,3-dioxygenase (IDO) are induced within cell-mediated (=Th1-type) immune response, and in patients with coronary artery disease, serum neopterin and the kynurenine to tryptophan ratio (Kyn/Trp) are significantly predictive for cardiovascular and total mortality. To examine the potential impact of vitamin K-antagonist acenocoumarol (Sintrom) on the inflammatory response we investigated its effect on freshly isolated peripheral blood mononuclear cells (PBMC) from healthy donors, on myelomonocytic THP1-Blue and on intestinal Caco-2 cells in vitro. PBMC were incubated with increasing doses of acenocoumarol, and after 30 min either left unstimulated or stimulated with the mitogen phytohemagglutinin (PHA). Concentrations of neopterin, tryptophan, kynurenine, interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α) were measured in supernatants of PBMC after 48 h. Caco-2 cells were stimulated with IFN-γ and Kyn/Trp was used as readout. In THP1-Blue cells, the induction of NF-κB dependent reporter gene expression upon stimulation with lipopolysaccharide (LPS) was determined as an indicator of pro-inflammatory response. Upon stimulation, all measured immune response markers increased significantly compared to unstimulated cells. Acenocoumarol had no effect in unstimulated cells but in PHA-stimulated PBMC tryptophan breakdown and the formation of neopterin, as well as IFN-γ and TNF-α, were dose-dependently suppressed at concentrations as low as 10 μg/ml. Likewise, acenocoumarol dose-dependently inhibited tryptophan breakdown in IFN-γ stimulated Caco-2 cells. Interestingly, NF-κB expression was super-induced in the LPS treated cells. Data suggest that the immunomodulatory capacity of acenocoumarol contributes to its therapeutic efficacy. SN - 1879-2472 UR - https://www.unboundmedicine.com/medline/citation/23481478/Immunomodulatory_effects_in_vitro_of_vitamin_K_antagonist_acenocoumarol_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0049-3848(13)00079-0 DB - PRIME DP - Unbound Medicine ER -