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215. Binding to Iron Quercetin Complexes Increases the Antioxidant Capacity of the Major Birch Pollen Allergen Bet v 1 and Reduces Its Allergenicity

Author

Regner, Andreas, Szepannek, Nathalie, Wiederstein, Markus, Fakhimahmadi, Aila, Paciosis, Luis F., Blokhuis, Bart R., Redegeld, Frank A., Hofstetter, Gerlinde, Dvorak, Zdenek, Jensen-Jarolim, Erika, Hufnagl, Karin, Roth-Walter, Franziska, Afd Pharmacology, Afd Pharmacology, Biomedical International R+D GmbH, Bencard Allergie GmbH, Danube Allergy Research Cluster-DARC, Karl-Landsteiner University, Wiederstein, Markus, Fakhimahmadi, Aila, Paciosis, Luis F., Blokhuis, Bart R., Redegeld, Frank A., Hofstetter, Gerlinde, Dvorak, Zdenek, Jensen-Jarolim, Erika, Hufnagl, Karin, and Roth-Walter, Franziska

Subjects
immune resilience, Salicylic-Acid, Receptor, Activation, Protein, Deficiency, Ige, Inhibition, Flavonoids, Mechanism, Immunity, Physiology, holo-Bet v 1, major allergen, immunomodulation, iron, quercetin, birch pollen, pathogenesis-related proteins, innate defense, nutritional immunity, Clinical Biochemistry, Cell Biology, Biochemistry, Molecular Biology, Food Science
Abstract

16 Pág., Bet v 1 is the major allergen in birch pollen to which up to 95% of patients sensitized to birch respond. As a member of the pathogenesis-related PR 10 family, its natural function is implicated in plant defense, with a member of the PR10 family being reported to be upregulated under iron deficiency. As such, we assessed the function of Bet v 1 to sequester iron and its immunomodulatory properties on human immune cells. Binding of Bet v 1 to iron quercetin complexes FeQ2 was determined in docking calculations and by spectroscopy. Serum IgE-binding to Bet v 1 with (holoBet v1) and without ligands (apoBet v 1) were assessed by ELISA, blocking experiments and Western Blot. Crosslinking-capacity of apo/holoBet v 1 were assessed on human mast cells and Arylhydrocarbon receptor (AhR) activation with the human reporter cellline AZ-AHR. Human PBMCs were stimulated and assessed for labile iron and phenotypic changes by flow cytometry. Bet v 1 bound to FeQ2 strongly with calculated Kd values of 1 nm surpassing affinities to quercetin alone nearly by a factor of 1000. Binding to FeQ2 masked IgE epitopes and decreased IgE binding up to 80% and impaired degranulation of sensitized human mast cells. Bet v 1 facilitated the shuttling of quercetin, which activated the anti-inflammatory AhR pathway and increased the labile iron pool of human monocytic cells. The increase of labile iron was associated with an anti-inflammatory phenotype in CD14+monocytes and downregulation of HLADR. To summarize, we reveal for the first time that FeQ2 binding reduces the allergenicity of Bet v 1 due to ligand masking, but also actively contributes anti-inflammatory stimuli to human monocytes, thereby fostering tolerance. Nourishing immune cells with complex iron may thus represent a promising antigen-independent immunotherapeutic approach to improve efficacy in allergen immunotherapy., The study was partly supported by Biomedical Int. R+D GmbH, Vienna, Austria and by Bencard Allergy GmbH, Munich, Germany. A.F. and K.H. were supported by the Danube Allergy Research Cluster-DARC #08 of the Karl-Landsteiner University, Krems, Austria, to E.J.-J.

Published
2023

216. Binding to Iron Quercetin Complexes Increases the Antioxidant Capacity of the Major Birch Pollen Allergen Bet v 1 and Reduces Its Allergenicity

Author

Biomedical International R+D GmbH, Bencard Allergie GmbH, Danube Allergy Research Cluster, Karl Landsteiner University of Health Sciences, Wiederstein, Markus [0000-0002-4750-4746], Fakhimahmadi, Aila [0000-0002-6804-6238], Pacios, Luis F. [0000-0002-0585-4289], Blokhuis, Bart R. [0000-0002-9366-6404], Redegeld, Frank A. [0000-0001-8830-7960], Hofstetter, Gerlinde [0000-0003-2077-4479], Dvorak, Zdenek [0000-0002-3938-3585], Jensen-Jarolim, Erika [0000-0003-4019-5765], Hufnagl, Karin [0000-0002-2288-2468], Roth-Walter, Franziska [0000-0001-5005-9228], Regner, Andreas, Szepannek, Nathalie, Wiederstein, Markus, Fakhimahmadi, Aila, Pacios, Luis F., Blokhuis, Bart R., Redegeld, Frank A., Hofstetter, Gerlinde, Dvorak, Zdenek, Jensen-Jarolim, Erika, Hufnagl, Karin, Roth-Walter, Franziska, Biomedical International R+D GmbH, Bencard Allergie GmbH, Danube Allergy Research Cluster, Karl Landsteiner University of Health Sciences, Wiederstein, Markus [0000-0002-4750-4746], Fakhimahmadi, Aila [0000-0002-6804-6238], Pacios, Luis F. [0000-0002-0585-4289], Blokhuis, Bart R. [0000-0002-9366-6404], Redegeld, Frank A. [0000-0001-8830-7960], Hofstetter, Gerlinde [0000-0003-2077-4479], Dvorak, Zdenek [0000-0002-3938-3585], Jensen-Jarolim, Erika [0000-0003-4019-5765], Hufnagl, Karin [0000-0002-2288-2468], Roth-Walter, Franziska [0000-0001-5005-9228], Regner, Andreas, Szepannek, Nathalie, Wiederstein, Markus, Fakhimahmadi, Aila, Pacios, Luis F., Blokhuis, Bart R., Redegeld, Frank A., Hofstetter, Gerlinde, Dvorak, Zdenek, Jensen-Jarolim, Erika, Hufnagl, Karin, and Roth-Walter, Franziska

Abstract

Bet v 1 is the major allergen in birch pollen to which up to 95% of patients sensitized to birch respond. As a member of the pathogenesis-related PR 10 family, its natural function is implicated in plant defense, with a member of the PR10 family being reported to be upregulated under iron deficiency. As such, we assessed the function of Bet v 1 to sequester iron and its immunomodulatory properties on human immune cells. Binding of Bet v 1 to iron quercetin complexes FeQ2 was determined in docking calculations and by spectroscopy. Serum IgE-binding to Bet v 1 with (holoBet v1) and without ligands (apoBet v 1) were assessed by ELISA, blocking experiments and Western Blot. Crosslinking-capacity of apo/holoBet v 1 were assessed on human mast cells and Arylhydrocarbon receptor (AhR) activation with the human reporter cellline AZ-AHR. Human PBMCs were stimulated and assessed for labile iron and phenotypic changes by flow cytometry. Bet v 1 bound to FeQ2 strongly with calculated Kd values of 1 nm surpassing affinities to quercetin alone nearly by a factor of 1000. Binding to FeQ2 masked IgE epitopes and decreased IgE binding up to 80% and impaired degranulation of sensitized human mast cells. Bet v 1 facilitated the shuttling of quercetin, which activated the anti-inflammatory AhR pathway and increased the labile iron pool of human monocytic cells. The increase of labile iron was associated with an anti-inflammatory phenotype in CD14+monocytes and downregulation of HLADR. To summarize, we reveal for the first time that FeQ2 binding reduces the allergenicity of Bet v 1 due to ligand masking, but also actively contributes anti-inflammatory stimuli to human monocytes, thereby fostering tolerance. Nourishing immune cells with complex iron may thus represent a promising antigen-independent immunotherapeutic approach to improve efficacy in allergen immunotherapy.

Published
2022

217. On Planar Boolean CSP

Author

Dvořák, Zdeněk, Kupec, Martin, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Halldórsson, Magnús M., editor, Iwama, Kazuo, editor, Kobayashi, Naoki, editor, and Speckmann, Bettina, editor

Published
2015
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221. Binding to Iron Quercetin Complexes Increases the Antioxidant Capacity of the Major Birch Pollen Allergen Bet v 1 and Reduces Its Allergenicity

Author

Afd Pharmacology, Regner, Andreas, Szepannek, Nathalie, Wiederstein, Markus, Fakhimahmadi, Aila, Paciosis, Luis F., Blokhuis, Bart R., Redegeld, Frank A., Hofstetter, Gerlinde, Dvorak, Zdenek, Jensen-Jarolim, Erika, Hufnagl, Karin, Roth-Walter, Franziska, Afd Pharmacology, Regner, Andreas, Szepannek, Nathalie, Wiederstein, Markus, Fakhimahmadi, Aila, Paciosis, Luis F., Blokhuis, Bart R., Redegeld, Frank A., Hofstetter, Gerlinde, Dvorak, Zdenek, Jensen-Jarolim, Erika, Hufnagl, Karin, and Roth-Walter, Franziska

Published
2023

222. A computational approach for finding 6-List-critical graphs on the Torus

Author

Universitat Politècnica de Catalunya. Departament de Matemàtiques, Univerzita Karlova, Dvorak, Zdenek, Moreno Peñarrubia, Félix, Universitat Politècnica de Catalunya. Departament de Matemàtiques, Univerzita Karlova, Dvorak, Zdenek, and Moreno Peñarrubia, Félix

Abstract

La coloració de grafs dibuixats a superfícies és un àrea antiga i molt estudiada de la teoria de grafs. Thomassen va demostrar que hi ha un nombre finit de grafs 6-crítics a qualsevol superfície fixa i va proporcionar el conjunt explícit dels grafs 6-crítics al torus. Després, Postle va demostrar que hi ha un nombre finit de grafs 6-llista-crítics a qualsevol superfície fixa. Amb l'objectiu de trobar el conjunt de grafs 6-llista-crítics al torus, desenvolupem i implementem tècniques algorítmiques per la cerca per ordinador de grafs crítics en diferents situacions de coloració per llistes., La coloración de grafos dibujados en superficies es un área antigua y muy estudiada de la teoría de grafos. Thomassen demostró que hay un número finito de grafos 6-críticos en cualquier superficie fija y proporcionó el conjunto explícito de los grafos 6-críticos en el toro. Después, Postle demostró que hay un número finito de grafos 6-lista-críticos en cualquier superficie fija. Con el objetivo de encontrar el conjunto de grafos 6-lista-críticos en el toro, desarrollamos e implementamos técnicas algorítmicas para la búsqueda por ordenador de grafos críticos en diferentes situaciones de coloración por listas., Coloring graphs embedded on surfaces is an old and well-studied area of graph theory. Thomassen proved that there are finitely many 6-critical graphs on any fixed surface and provided the explicit set of 6-critical graphs on the torus. Later, Postle proved that there are finitely many 6-list-critical graphs on any fixed surface. With the goal of finding the set of 6-list-critical graphs on the torus, we develop and implement algorithmic techniques for computer search of critical graphs in different list-coloring settings., Outgoing

Published
2023

228. A Dynamic Data Structure for MSO Properties in Graphs with Bounded Tree-Depth

Author

Dvořák, Zdeněk, Kupec, Martin, Tůma, Vojtěch, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Kobsa, Alfred, Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Schulz, Andreas S., editor, and Wagner, Dorothea, editor

Published
2014
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229. Large Independent Sets in Triangle-Free Planar Graphs

Author

Dvořák, Zdeněk, Mnich, Matthias, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Kobsa, Alfred, Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Schulz, Andreas S., editor, and Wagner, Dorothea, editor

Published
2014
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231. A Dynamic Data Structure for Counting Subgraphs in Sparse Graphs

Author

Dvořák, Zdeněk, Tůma, Vojtěch, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Dehne, Frank, editor, Solis-Oba, Roberto, editor, and Sack, Jörg-Rüdiger, editor

Published
2013
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234. Binding to Iron Quercetin Complexes Increases the Antioxidant Capacity of the Major Birch Pollen Allergen Bet v 1 and Reduces Its Allergenicity

Author

Regner, Andreas, primary, Szepannek, Nathalie, additional, Wiederstein, Markus, additional, Fakhimahmadi, Aila, additional, Paciosis, Luis F., additional, Blokhuis, Bart R., additional, Redegeld, Frank A., additional, Hofstetter, Gerlinde, additional, Dvorak, Zdenek, additional, Jensen-Jarolim, Erika, additional, Hufnagl, Karin, additional, and Roth-Walter, Franziska, additional

Published
2022
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235. Algorithms for Classes of Graphs with Bounded Expansion

Author

Dvořák, Zdeněk, Král’, Daniel, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Paul, Christophe, editor, and Habib, Michel, editor

Published
2010
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239. On the Complexity of the G-Reconstruction Problem

Author

Dvořák, Zdeněk, Jelínek, Vít, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Deng, Xiaotie, editor, and Du, Ding-Zhu, editor

Published
2005
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240. Three Optimal Algorithms for Balls of Three Colors

Author

Dvořák, Zdeněk, Jelínek, Vít, Král’, Daniel, Kynčl, Jan, Saks, Michael, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Diekert, Volker, editor, and Durand, Bruno, editor

Published
2005
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241. Micronutritional supplementation with a holoBLG-based FSMP (food for special medical purposes)-lozenge alleviates allergic symptoms in BALB/c mice: Imitating the protective farm effect

Author

Biomedical International R+D GmbH, Austrian Science Fund, Bencard Allergie GmbH, Afify, Sheriene Moussa [0000-0003-2082-9038], Pacios, Luis F [0000-0002-0585-4289], Redegeld, Frank A. [0000-0001-8830-7960], Pali-Schöll, Isabella [0000-0003-2089-6011], Hufnagl, Karin [0000-0002-2288-2468], Bianchini, Rodolfo [0000-0003-0351-6937], Guethoff, Sonja [0000-0001-5846-1035], Kramer, Matthias F [0000-0002-3740-4733], Fiocchi, Alessandro [0000-0002-2549-0523], Dvorak, Zdenek [0000-0002-3938-3585], Jensen-Jarolim, Erika [0000-0003-4019-5765], Roth-Walter, Franziska [0000-0001-5005-9228], Afify, Sheriene Moussa, Regner, Andreas, Pacios, Luis F., Blokhuis, Bart R., Jensen, Sebastian A, Redegeld, Frank A., Pali-Schöll, Isabella, Hufnagl, Karin, Bianchini, Rodolfo, Guethoff, Sonja, Kramer, Matthias F, Fiocchi, Alessandro, Dvorak, Zdenek, Jensen-Jarolim, Erika, Roth-Walter, Franziska, Biomedical International R+D GmbH, Austrian Science Fund, Bencard Allergie GmbH, Afify, Sheriene Moussa [0000-0003-2082-9038], Pacios, Luis F [0000-0002-0585-4289], Redegeld, Frank A. [0000-0001-8830-7960], Pali-Schöll, Isabella [0000-0003-2089-6011], Hufnagl, Karin [0000-0002-2288-2468], Bianchini, Rodolfo [0000-0003-0351-6937], Guethoff, Sonja [0000-0001-5846-1035], Kramer, Matthias F [0000-0002-3740-4733], Fiocchi, Alessandro [0000-0002-2549-0523], Dvorak, Zdenek [0000-0002-3938-3585], Jensen-Jarolim, Erika [0000-0003-4019-5765], Roth-Walter, Franziska [0000-0001-5005-9228], Afify, Sheriene Moussa, Regner, Andreas, Pacios, Luis F., Blokhuis, Bart R., Jensen, Sebastian A, Redegeld, Frank A., Pali-Schöll, Isabella, Hufnagl, Karin, Bianchini, Rodolfo, Guethoff, Sonja, Kramer, Matthias F, Fiocchi, Alessandro, Dvorak, Zdenek, Jensen-Jarolim, Erika, and Roth-Walter, Franziska

Abstract

Previously, the protective farm effect was imitated using the whey protein beta-lactoglobulin (BLG) that is spiked with iron-flavonoid complexes. Here, we formulated for clinical translation a lozenge as food for special medical purposes (FSMP) using catechin-iron complexes as ligands for BLG. The lozenge was tested in vitro and in a therapeutical BALB/c mice model.

Published
2021

242. Locally Consistent Constraint Satisfaction Problems

Author

Dvořák, Zdeněk, Král’, Daniel, Pangrác, Ondřej, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Díaz, Josep, editor, Karhumäki, Juhani, editor, Lepistö, Arto, editor, and Sannella, Donald, editor

Published
2004
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243. An Algorithm for Cyclic Edge Connectivity of Cubic Graphs : (Extended Abstract)

Author

Dvořák, Zdeněk, Kára, Jan, Král’, Daniel, Pangrác, Ondřej, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Hagerup, Torben, editor, and Katajainen, Jyrki, editor

Published
2004
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