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22 results on '"Wiederstein, Markus"'

1. Mould allergen Alt a 1 spiked with the micronutrient retinoic acid reduces Th2 response and ameliorates Alternaria allergy in BALB/c mice.

Author

Fakhimahmadi, Aila, Roth‐Walter, Franziska, Hofstetter, Gerlinde, Wiederstein, Markus, Jensen, Sebastian A., Berger, Markus, Szepannek, Nathalie, Bianchini, Rodolfo, Pali‐Schöll, Isabella, Jensen‐Jarolim, Erika, and Hufnagl, Karin

Subjects
ALTERNARIA alternata, MOLECULAR docking, ALTERNARIA, ALLERGENS, EPITOPES, TRETINOIN
Abstract

Background: We investigated the biological function of the mould allergen Alt a 1 as a carrier of micronutrients, such as the vitamin A metabolite retinoic acid (RA) and the influence of RA binding on its allergenicity in vitro and in vivo. Methods: Alt a 1‐RA complex formation was analyzed in silico and in vitro. PBMCs from Alternaria‐allergic donors were stimulated with Alt a 1 complexed with RA (holo‐Alt a 1) or empty apo‐Alt a 1 and analyzed for cytokine production and CD marker expression. Serum IgE‐binding and crosslinking assays to apo‐ and holo‐protein were correlated to B‐cell epitope analysis. Female BALB/c mice already sensitized to Alt a 1 were intranasally treated with apo‐Alt a 1, holo‐Alt a 1 or RA alone before measuring anaphylactic response, serum antibody levels, splenic cytokines and CD marker expression. Results: In silico docking calculations and in vitro assays showed that the extent of RA binding depended on the higher quaternary state of Alt a 1. Holo‐Alt a 1 loaded with RA reduced IL‐13 released from PBMCs and CD3+CD4+CRTh2 cells. Complexing Alt a 1 to RA masked its IgE B‐cell epitopes and reduced its IgE‐binding capacity. In a therapeutic mouse model of Alternaria allergy nasal application of holo‐Alt a 1, but not of apo‐Alt a 1, significantly impeded the anaphylactic response, impaired splenic antigen‐presenting cells and induced IL‐10 production. Conclusion: Holo‐Alt a 1 binding to RA was able to alleviate Th2 immunity in vitro, modulate an ongoing Th2 response and prevent anaphylactic symptoms in vivo, presenting a novel option for improving allergen‐specific immunotherapy in Alternaria allergy. [ABSTRACT FROM AUTHOR]

Published
2024
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2. IMPI: An Interface for Low-Frequency Point Mutation Identification Exemplified on Resistance Mutations in Chronic Myeloid Leukemia.

Author

Vetter, Julia, Burghofer, Jonathan, Malli, Theodora, Lin, Anna M., Webersinke, Gerald, Wiederstein, Markus, Winkler, Stephan M., and Schaller, Susanne

Subjects
POINT mutation (Biology), CHRONIC myeloid leukemia, CANCER treatment, QUALITY control, DNA sequencing
Abstract

Background: In genomics, highly sensitive point mutation detection is particularly relevant for cancer diagnosis and early relapse detection. Next-generation sequencing combined with unique molecular identifiers (UMIs) is known to improve the mutation detection sensitivity. Methods: We present an open-source bioinformatics framework named Interface for Point Mutation Identification (IMPI) with a graphical user interface (GUI) for processing especially small-scale NGS data to identify variants. IMPI ensures detailed UMI analysis and clustering, as well as initial raw read processing, and consensus sequence building. Furthermore, the effects of custom algorithm and parameter settings for NGS data pre-processing and UMI collapsing (e.g., UMI clustered versus unclustered (raw) reads) can be investigated. Additionally, IMPI implements optimization and quality control methods; an evolution strategy is used for parameter optimization. Results: IMPI was designed, implemented, and tested using BCR::ABL1 fusion gene kinase domain sequencing data. In summary, IMPI enables a detailed analysis of the impact of UMI clustering and parameter setting changes on the measured allele frequencies. Conclusions: Regarding the BCR::ABL1 data, IMPI's results underlined the need for caution while designing specialized single amplicon NGS approaches due to methodical limitations (e.g., high PCR-mediated recombination rate). This cannot be corrected using UMIs. [ABSTRACT FROM AUTHOR]

Published
2024
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3. 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

4. Nutritional Provision of Iron Complexes by the Major Allergen Alt a 1 to Human Immune Cells Decreases Its Presentation.

Author

Fakhimahmadi, Aila, Hasanaj, Ilir, Hofstetter, Gerlinde, Pogner, Clara, Gorfer, Markus, Wiederstein, Markus, Szepannek, Nathalie, Bianchini, Rodolfo, Dvorak, Zdenek, Jensen, Sebastian A., Berger, Markus, Jensen-Jarolim, Erika, Hufnagl, Karin, and Roth-Walter, Franziska

Subjects
QUATERNARY structure, ALLERGENS, ALTERNARIA alternata, IRON, PROTEIN binding, ALANINE aminotransferase, CASEINS
Abstract

Alternaria alternata is a common fungus strongly related with severe allergic asthma, with 80% of affected individuals being sensitized solely to its major allergen Alt a 1. Here, we assessed the function of Alt a 1 as an innate defense protein binding to micronutrients, such as iron–quercetin complexes (FeQ2), and its impact on antigen presentation in vitro. Binding of Alt a 1 to FeQ2 was determined in docking calculations. Recombinant Alt a 1 was generated, and binding ability, as well as secondary and quaternary structure, assessed by UV-VIS, CD, and DLS spectroscopy. Proteolytic functions were determined by casein and gelatine zymography. Uptake of empty apo– or ligand-filled holoAlt a 1 were assessed in human monocytic THP1 cells under the presence of dynamin and clathrin-inhibitors, activation of the Arylhydrocarbon receptor (AhR) using the human reporter cellline AZ-AHR. Human PBMCs were stimulated and assessed for phenotypic changes in monocytes by flow cytometry. Alt a 1 bound strongly to FeQ2 as a tetramer with calculated Kd values reaching pico-molar levels and surpassing affinities to quercetin alone by a factor of 5000 for the tetramer. apoAlt a 1 but not holoAlta 1 showed low enzymatic activity against casein as a hexamer and gelatin as a trimer. Uptake of apo– and holo–Alt a 1 occurred partly clathrin-dependent, with apoAlt a 1 decreasing labile iron in THP1 cells and holoAlt a 1 facilitating quercetin-dependent AhR activation. In human PBMCs uptake of holoAlt a 1 but not apoAlt a 1 significantly decreased the surface expression of the costimulatory CD86, but also of HLADR, thereby reducing effective antigen presentation. We show here for the first time that the presence of nutritional iron complexes, such as FeQ2, significantly alters the function of Alt a 1 and dampens the human immune response, thereby supporting the notion that Alt a 1 only becomes immunogenic under nutritional deprivation. [ABSTRACT FROM AUTHOR]

Published
2023
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5. 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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6. Backbone distortions in lactam‐bridged helical peptides

Author

Moazzam, Ali, primary, Stanojlovic, Vesna, additional, Hinterholzer, Arthur, additional, Holzner, Christoph, additional, Roschger, Cornelia, additional, Zierer, Andreas, additional, Wiederstein, Markus, additional, Schubert, Mario, additional, and Cabrele, Chiara, additional

Published
2022
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7. Bet v 1 from birch pollen is a hypoallergen with vitamin D3 in the pocket

Author

Hufnagl, Karin, primary, Kromp, Livia, additional, Bianchini, Rodolfo, additional, Afify, Sheriene Moussa, additional, Wiederstein, Markus, additional, Redegeld, Frank A., additional, Zuvalova, Iveta, additional, Dvorak, Zdenek, additional, Hofstetter, Gerlinde, additional, Roth‐Walter, Franziska, additional, Pacios, Luis F., additional, and Jensen‐Jarolim, Erika, additional

Published
2021
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8. Disease-related blood-based differential methylation in cystic fibrosis and its representation in lung cancer revealed a regulatory locus in PKP3 in lung epithelial cells

Author

Schamschula, Esther, primary, Lahnsteiner, Angelika, additional, Assenov, Yassen, additional, Hagmann, Wolfgang, additional, Zaborsky, Nadja, additional, Wiederstein, Markus, additional, Strobl, Anna, additional, Stanke, Frauke, additional, Muley, Thomas, additional, Plass, Christoph, additional, Tümmler, Burkhard, additional, and Risch, Angela, additional

Published
2021
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10. Journal of Peptide Science / Backbone distortions in lactam-bridged helical peptides

Author

Moazzam, Ali, Stanojlovic, Vesna, Hinterholzer, Arthur, Holzner, Christoph, Roschger, Cornelia, Zierer, Andreas, Wiederstein, Markus, Schubert, Mario, and Cabrele, Chiara

Subjects
carbonyl tilting, NMR spectroscopy, lactam bridge, circular dichroism, α-helix
Abstract

Side-chain-to-side-chain cyclization is frequently used to stabilize the α-helical conformation of short peptides. In a previous study, we incorporated a lactam bridge between the side chains of Lys-i and Asp-i+4 in the nonapeptide 1Y, cyclo-(2,6)-(Ac-VKRLQDLQY-NH2), an artificial ligand of the inhibitor of DNA binding and cell differentiation (ID) protein with antiproliferative activity on cancer cells. Herein, we show that only the cyclized five-residue segment adopts a helical turn whereas the C-terminal residues remain flexible. Moreover, we present nine 1Y analogs arising from different combinations of hydrophobic residues (leucine, isoleucine, norleucine, valine, and tyrosine) at positions 1, 4, 7, and 9. All cyclopeptides except one build a lactam-bridged helical turn; however, residue-4 reveals less helix character than the neighboring Arg-3 and Gln-5, especially with residue-4 being isoleucine, valine, and tyrosine. Surprisingly, only two cyclopeptides exhibit helix propagation until the C-terminus, whereas the others share a remarkable outward tilting of the backbone carbonyl of the lactam-bridged Asp-6 (>40° deviation from the orientation parallel to the helix axis), which prevents the formation of the H-bond between Arg-3 CO and residue-7 NH: As a result, the propagation of the helix beyond the lactam-bridged sequence becomes unfavorable. We conclude that, depending on the amino-acid sequence, the lactam bridge between Lys-i and Asp-i+4 can stabilize a helical turn but deviations from the ideal helix geometry are possible: Indeed, besides the outward tilting of the backbone carbonyls, the residues per turn increased from 3.6 (typical of a regular α-helix) to 4.2, suggesting a partial helix unwinding.

Published
2021

11. Disease-related blood-based differential methylation in cystic fibrosis and its representation in lung cancer revealed a regulatory locus in PKP3 in lung epithelial cells.

Author

Schamschula, Esther, Lahnsteiner, Angelika, Assenov, Yassen, Hagmann, Wolfgang, Zaborsky, Nadja, Wiederstein, Markus, Strobl, Anna, Stanke, Frauke, Muley, Thomas, Plass, Christoph, Tümmler, Burkhard, and Risch, Angela

Subjects
CYSTIC fibrosis, LUNG cancer, PULMONARY fibrosis, LUNGS, EPITHELIAL cells, TWINS, MOVEMENT sequences
Abstract

Cystic fibrosis (CF) is a monogenic disease, characterized by massive chronic lung inflammation. The observed variability in clinical phenotypes in monozygotic CF twins is likely associated with the extent of inflammation. This study sought to investigate inflammation-related aberrant DNA methylation in CF twins and to determine to what extent acquired methylation changes may be associated with lung cancer. Blood-based genome-wide DNA methylation analysis was performed to compare the DNA methylomes of monozygotic twins, from the European CF Twin and Sibling Study with various degrees of disease severity. Putatively inflammation-related and differentially methylated positions were selected from a large lung cancer case-control study and investigated in blood by targeted bisulphite next-generation-sequencing. An inflammation-related locus located in the Plakophilin-3 (PKP3) gene was functionally analysed regarding promoter and enhancer activity in presence and absence of methylation using luciferase reporter assays. We confirmed in a unique cohort that monozygotic twins, even if clinically discordant, have only minor differences in global DNA methylation patterns and blood cell composition. Further, we determined the most differentially methylated positions, a high proportion of which are blood cell-type-specific, whereas others may be acquired and thus have potential relevance in the context of inflammation as lung cancer risk factors. We identified a sequence in the gene body of PKP3 which is hypermethylated in blood from CF twins with severe phenotype and highly variably methylated in lung cancer patients and controls, independent of known clinical parameters, and showed that this region exhibits methylation-dependent promoter activity in lung epithelial cells. [ABSTRACT FROM AUTHOR]

Published
2022
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13. Disease-related blood-based differential methylation in cystic fibrosis and its representation in lung cancer revealed a regulatory locus in PKP3in lung epithelial cells

Author

Schamschula, Esther, Lahnsteiner, Angelika, Assenov, Yassen, Hagmann, Wolfgang, Zaborsky, Nadja, Wiederstein, Markus, Strobl, Anna, Stanke, Frauke, Muley, Thomas, Plass, Christoph, Tümmler, Burkhard, and Risch, Angela

Abstract

ABSTRACTCystic fibrosis (CF) is a monogenic disease, characterized by massive chronic lung inflammation. The observed variability in clinical phenotypes in monozygotic CF twins is likely associated with the extent of inflammation. This study sought to investigate inflammation-related aberrant DNA methylation in CF twins and to determine to what extent acquired methylation changes may be associated with lung cancer.Blood-based genome-wide DNA methylation analysis was performed to compare the DNA methylomes of monozygotic twins, from the European CF Twin and Sibling Study with various degrees of disease severity. Putatively inflammation-related and differentially methylated positions were selected from a large lung cancer case-control study and investigated in blood by targeted bisulphite next-generation-sequencing. An inflammation-related locus located in the Plakophilin-3(PKP3) gene was functionally analysed regarding promoter and enhancer activity in presence and absence of methylation using luciferase reporter assays.We confirmed in a unique cohort that monozygotic twins, even if clinically discordant, have only minor differences in global DNA methylation patterns and blood cell composition. Further, we determined the most differentially methylated positions, a high proportion of which are blood cell-type-specific, whereas others may be acquired and thus have potential relevance in the context of inflammation as lung cancer risk factors. We identified a sequence in the gene body of PKP3which is hypermethylated in blood from CF twins with severe phenotype and highly variably methylated in lung cancer patients and controls, independent of known clinical parameters, and showed that this region exhibits methylation-dependent promoter activity in lung epithelial cells.

Published
2022
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15. Oncogenic GLI1 and STAT1/3 activation drives immunosuppressive tryptophan/kynurenine metabolism via synergistic induction of IDO1 in skin cancer cells

Author

Elmer, Dominik P., primary, Strobl, Victoria, additional, Stockmaier, Georg, additional, Dang, Hieu-Hoa, additional, Wiederstein, Markus, additional, Licha, David, additional, Strobl, Anna, additional, Sternberg, Christina, additional, Tesanovic, Suzana, additional, Grund-Groeschke, Sandra, additional, Gruber, Wolfgang, additional, Wolff, Florian, additional, Moriggl, Richard, additional, Risch, Angela, additional, Reischl, Roland, additional, Huber, Christian G., additional, Horejs-Hoeck, Jutta, additional, and Aberger, Fritz, additional

Published
2020
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16. Retinoic acid‐loading of the major birch pollen allergen Bet v 1 may improve specific allergen immunotherapy: In silico, in vitro and in vivo data in BALB/c mice

Author

Hufnagl, Karin, primary, Afify, Sheriene Moussa, additional, Braun, Nina, additional, Wagner, Stefanie, additional, Wallner, Michael, additional, Hauser, Michael, additional, Wiederstein, Markus, additional, Gadermaier, Gabriele, additional, Wildner, Sabrina, additional, Redegeld, Frank A., additional, Blokhuis, Bart R., additional, Hofstetter, Gerlinde, additional, Pali‐Schöll, Isabella, additional, Roth‐Walter, Franziska, additional, Pacios, Luis F., additional, and Jensen‐Jarolim, Erika, additional

Published
2020
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17. International Journal of Cancer / Synergistic crosstalk of hedgehog and interleukin6 signaling drives growth of basal cell carcinoma

Author

Sternberg, Christina, Gruber, Wolfgang, Eberl, Markus, Tesanovic, Suzana, Stadler, Manuela, Elmer, Dominik P., Schlederer, Michaela, Grund, Sandra, Roos, Simone, Wolff, Florian, Kaur, Supreet, Mangelberger, Doris, Lehrach, Hans, Hache, Hendrik, Wierling, Christoph, Laimer, Josef, Lackner, Peter, Wiederstein, Markus, Kasper, Maria, Risch, Angela, Petzelbauer, Peter, Moriggl, Richard, Kenner, Lukas, and Aberger, Fritz

Subjects
animal structures, integumentary system, basal cell carcinoma, hedgehog, GLI signaling, STAT transcription factors, skin and connective tissue diseases, GLI transcription factors, interleukin6 signaling
Abstract

Persistent activation of hedgehog (HH)/GLI signaling accounts for the development of basal cell carcinoma (BCC), a very frequent nonmelanoma skin cancer with rising incidence. Targeting HH/GLI signaling by approved pathway inhibitors can provide significant therapeutic benefit to BCC patients. However, limited response rates, development of drug resistance, and severe side effects of HH pathway inhibitors call for improved treatment strategies such as rational combination therapies simultaneously inhibiting HH/GLI and cooperative signals promoting the oncogenic activity of HH/GLI. In this study, we identified the interleukin6 (IL6) pathway as a novel synergistic signal promoting oncogenic HH/GLI via STAT3 activation. Mechanistically, we provide evidence that signal integration of IL6 and HH/GLI occurs at the level of cisregulatory sequences by cobinding of GLI and STAT3 to common HHIL6 target gene promoters. Genetic inactivation of Il6 signaling in a mouse model of BCC significantly reduced in vivo tumor growth by interfering with HH/GLIdriven BCC proliferation. Our genetic and pharmacologic data suggest that combinatorial HHIL6 pathway blockade is a promising approach to efficiently arrest cancer growth in BCC patients. (VLID)3012344

Published
2018

18. Synergistic cross-talk of hedgehog and interleukin-6 signaling drives growth of basal cell carcinoma

Author

Sternberg, Christina, primary, Gruber, Wolfgang, additional, Eberl, Markus, additional, Tesanovic, Suzana, additional, Stadler, Manuela, additional, Elmer, Dominik P., additional, Schlederer, Michaela, additional, Grund, Sandra, additional, Roos, Simone, additional, Wolff, Florian, additional, Kaur, Supreet, additional, Mangelberger, Doris, additional, Lehrach, Hans, additional, Hache, Hendrik, additional, Wierling, Christoph, additional, Laimer, Josef, additional, Lackner, Peter, additional, Wiederstein, Markus, additional, Kasper, Maria, additional, Risch, Angela, additional, Petzelbauer, Peter, additional, Moriggl, Richard, additional, Kenner, Lukas, additional, and Aberger, Fritz, additional

Published
2018
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19. Particle and Fibre Toxicology / Nanoparticle-allergen interactions mediate human allergic responses : protein corona characterization and cellular responses

Author

Radauer-Preiml, Isabella, Andosch, Ancuela, Hawranek, Thomas, Luetz-Meindl, Ursula, Wiederstein, Markus, Horejs-Höck, Jutta, Himly, Martin, Boyles, Matthew, and Duschl, Albert

Subjects
Allergy, Protein corona, Gold nanoparticles, A549 cells, Basophil activation, Protease activity, respiratory tract diseases
Abstract

Background: Engineered nanomaterials (ENMs) interact with different biomolecules as soon as they are in contact, resulting in the formation of a biomolecule ‘corona. Hence, the ‘corona defines the biological identity of the ENMs and could affect the response of the immune system to ENM exposure. With up to 40 % of the world population suffering from type I allergy, a possible modulation of allergen effects by binding to ENMs is highly relevant with respect to work place and consumer safety. Therefore, the aim of this present study was to gain an insight into the interactions of gold nanoparticles with different seasonally and perennially occurring outdoor and indoor allergens. Methods: Gold nanoparticles (AuNPs) were conjugated with the major allergens of birch pollen (Bet v 1), timothy grass pollen (Phl p 5) and house dust mite (Der p 1). The AuNP-allergen conjugates were characterized by means of TEM negative staining, dynamic light scattering (DLS), z-potential measurements and hyperspectral imaging. Furthermore, 3D models were constructed, based on the characterization data, to visualize the interaction between the allergens and the AuNPs surface. Differences in the activation of human basophil cells derived from birch/grass pollen- and house dust mite-allergic patients in response to free allergen and AuNP-allergen conjugates were determined using the basophil activation assay (BAT). Potential allergen corona replacement during BAT was controlled for using Western blotting. The protease activity of AuNP-Der p 1 conjugates compared to free Der p 1 was assessed, by an enzymatic activity assay and a cellular assay pertaining to lung type II alveolar epithelial cell tight junction integrity. Results: The formation of a stable corona was found for all three allergens used. Our data suggest, that depending on the allergen, different effects are observed after binding to ENMs, including enhanced allergic responses against Der p 1 and also, for some patients, against Bet v 1. Moreover elevated protease activity of AuNP-Der p 1 conjugates compared to free Der p 1 was found. Conclusion: In summary, this study presents that conjugation of allergens to ENMs can modulate the human allergic response, and that protease activity can be increased. FP7 263147

Published
2016

20. WAO International Scientific Conference (WISC 2016) Abstracts

Author

Bao, Jun, Wang, Yi-Hui, Liu, Quan-Hua, Bao, Yi-Xiao, Azouz, Nurit, Caldwell, Julie, Ray, Leanne, Rochman, Mark, Mingler, Melissa, Eilerman, Matthew, Wen, Ting, Myers, Jocelyn Biagini, Hershey, Gurjit Khurana, Kottyan, Leah, Martin, Lisa, Marc, Rothenberg, Gonzalez-Uribe, Victor, Del Rio-Chivardi, Jaime, Del Rio-Navarro, Blanca, Lou, Hongfei, Ma, Siyuan, Zhao, Yan, Cao, Feifei, He, Fei, Liu, Zhongyan, Wang, Chengshuo, Bachert, Claus, Zhang, Luo, Abrams, Elissa, Becker, Allan, Kandhare, Amit, Bodhankar, Subhash, Grossman, Nicole, Doros, Gheorghe, Laden, Francine, Fuhlbrigge, Anne, Wechsler, Michael, Pace, Wilson, Yawn, Barbara, Israel, Elliot, Lee, Junehyuk, Adler, Frederick, Kim, Peter, Huang, Yung Feng, Chen, Ying Yao, Pan, Chiun Yen, Lee, Herng Sheng, Khalemsky, Michael, Schwartz, David G., Kolkhir, Pavel, Pogorelov, Dmitry, Kochergin, Nikolay, Komarow, Hirsh, Young, Michael, Eisch, Robin, Scott, Linda, Metcalfe, Dean, Singer, Alexander, Wakeman, Andrew, Gerstner, Thomas, Song, Woo-Jung, Shim, Ji-Su, Won, Ha-Kyeong, Kang, Sung-Yoon, Sohn, Kyoung-Hee, Kim, Byung-Keun, Jo, Eun-Jung, Kim, Min-Hye, Kim, Sang-Heon, Park, Heung-Woo, Kim, Sun-Sin, Chang, Yoon-Seok, Morice, Alyn H., Lee, Byung-Jae, Cho, Sang-Heon, Min, Kyung-Up, Boscolo, Maria Assunta, Brivio, Giulio, Bosisio, Sergio, Manzocchi, Nicoletta, Pulixi, Edoardo, Grignani, Giulia, D’Andrea, Eloisia, Ricci, Massimo, Passini, Elena, Italia, Maurizio, Urrutia-Pereira, Marilyn, Fagundes, Stefani, Oliano, Vinicius Jardim, Solé, Dirceu, Benzaquen, Sadia, Aragaki, Alejandro, Balestra, Ricardo, Harden, Dawn, Caudell-Stamper, Danielle, Glady, Gilbert, Holbreich, Mark, Lyakhovska, Nataliya, Kaidashev, Igor, Bystron, Jaromir, Hutyrova, Beata, Balakirski, Galina, Vanstreels, Luk, Wurpts, Gerda, Merk, Hans F., Baron, Jens Malte, Plange, Johanna, Rihs, Hans-Peter, Raulf, Monika, Roeseler, Stefani, Tolcachier, Alberto, Chamorro, Armando, Otero, Ruth, Brooks, Joel, Hess, Michael, Benz, Jared, MacDonald, Joseph, Chatha, Usma, Lent, Dale, Köse, Şükran, Tatar, Bengü Gireniz, Akkoçlu, Gülgün, Çukurova, İbrahim, Ödemiş, İlker, Toker, Ayşin Kılınç, Hasssan, Abdullahi, Gobir, Abdulrazaq Abdullahi, Kim, Cheol-Woo, Choi, Young Hwa, Lee, Jeong Hye, Cho, Rae Jeong, Nam, Yu Ran, Nam, Joo Hyun, Kim, Woo Kyung, Filipovic, Ivana, Zivkovic, Zorica, Filipovic, Djordje, Shik, Dana, Smith, Andrew, Hsi, Wang Yui, Friedman, Stuart, Gizaw, Yonatan, Bakhda, Rima, Mohammed, Kumail, Wasserman, Richard, Hague, Angela, Pence, Deanna, Rolen, Joanna, Sugerman, Robert, Silvers, Stacy, Kamili, Qurat, Knauer, Nadezhda, Zazernyi, Alexandr, Blinova, Elena, Demina, Daria, Kozlov, Vladimir, Agrawal, Komal, Kale, Sagar, Arora, Naveen, Vasilkova, Volha, Mokhort, Tatiana, Silvers, William, Eisenberg, Rachel, Mehta, Rushita, Rubinstein, Arye, Aston, Antony, Turner, Paul, Ruiz-Garcia, Monica, Boyle, Robert, Brown, Simon, Schejter, Yael Dinur, Ovadia, Adi, Kim, Vy, Reid, Brenda, Roifman, Chaim, Rosenfield, Lana, Avilla, Ernie, Harada, Laurie, Allen, Marilyn, Waserman, Susan, Yoon, Ho Joo, Koo, Gun Woo, Chang, Suk-Il, Yoon, Hye-Ran, Park, Dong Won, Park, Tai Sun, Moon, Ji-Yong, Kim, Tae Hyung, Sohn, Jang Won, Shin, Dong Ho, Jorjoliani, Tsici, Jorjoliani, Lia, Adamia, Nino, katamadze, Nona, Ramachandra, Deepika, Jorjoliani, Liana, Karseladze, Rusudan, Saginadze, Lali, Chkuaseli, Natalia, Dolgova, Anna, Stukolova, Olga, Sudina, Anna, Cherkashina, Anna, Shipulin, German, Rosenthal, Richard, Howe, Harvey, Knause, Paul, Greemberg, Rony, De Bruycker, Jean Jacques, Fernandez, Isabel, Le Deist, Françoise, Haddad, Elie, Rha, Yeong Ho, Lee, Kyung Suk, Choi, Sun Hee, Tam, Herman, Simons, Estelle, Simons, Elinor, Golebiowska-Wawrzyniak, Maria, Markiewicz, Katarzyna, Faitelson, Yoram, Stein, Miguel, Mandelberg, Avigdor, Dalal, Ilan, Levin, Michael, Hobane, Lelani, Basera, Wisdom, Botha, Maresa, Gray, Claudia, Zar, Heather, Kjaeva, Biserka Jovkovska, Arsovski, Zoran, Grivcheva-Panovska, Vesna, Odebode, Adeyinka, Adekunle, 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Bianchini, Rodolfo, Roth-Walter, Franziska, Ohradanova-Repic, Anna, Hofstetter, Gerlinde, Herrmann, Ina, Carvalho, Maria Isabel, Hufnagl, Karin, Bajna, Erika, Roth, Georg, Stockinger, Hannes, Jensen-Jarolim, Erika, Almog, Meital, Kessel, Aharon, Apov, Larisa, Salguero, Carlos Sanchez, Chacon, Alvaro Sanchez, Nazarov, Abbos, Ergashev, Shaxbos, Nesterova, Irina, Kovaleva, Svetlana, Chudilova, Galina, Lomtatidze, Ludmila, De Schryver, Sarah, Dery, Alizee, Clarke, Ann, Nadeau, Kari, Weatherall, Kimberly, Greenwood, Celia, Daley, Denise, Asai, Yuka, Ben-Shoshan, Moshe, Balmasova, Irina, Malova, Elena, Wagner, Stefanie, Pacios, Luis F., Wallner, Michael, Wiederstein, Markus, Tevs, Anna E., Tataurshchikova, Nataly, Sangidorj, Baigalmaa, Ronzhina, Anna, Chikhladze, Manana, Wirz, Oliver F., van de Veen, Willem, Mirer, David, Morita, Hideaki, Altunbulakli, Can, Johnston, Sebastian L., Glanville, Nicholas, Papadopoulos, Nikolaos G., Akdis, Cezmi A., Akdis, Mübeccel, Reshef, Avner, Riedl, Marc, Panovska, Vesna Grivcheva, Moldovan, Dumitru, Baker, James, Yang, William H., Andrejevic, Sladjana, Lockey, Richard F., Hakl, Roman, Kivity, Shmuel, Bellizzi, Luca, Harper, Joseph R., Relan, Anurag, and Cicardi, Marco

Subjects
lcsh:Immunologic diseases. Allergy, Pulmonary and Respiratory Medicine, 010504 meteorology & atmospheric sciences, business.industry, Immunology, Library science, Meeting Abstracts, 01 natural sciences, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Immunology and Allergy, Medicine, lcsh:RC581-607, business, 0105 earth and related environmental sciences, Wechsler Intelligence Scale for Children
Published
2017

22. Nanoparticle-allergen interactions mediate human allergic responses: protein corona characterization and cellular responses.

Author

Radauer-Preiml, Isabella, Andosch, Ancuela, Hawranek, Thomas, Luetz-Meindl, Ursula, Wiederstein, Markus, Horejs-Hoeck, Jutta, Himly, Martin, Boyles, Matthew, and Duschl, Albert

Subjects
NANOPARTICLES analysis, ALLERGENS, BIOMOLECULE analysis, IMMUNE system, CARRIER proteins, GOLD nanoparticles
Abstract

Background: Engineered nanomaterials (ENMs) interact with different biomolecules as soon as they are in contact, resulting in the formation of a biomolecule 'corona'. Hence, the 'corona' defines the biological identity of the ENMs and could affect the response of the immune system to ENM exposure. With up to 40 % of the world population suffering from type I allergy, a possible modulation of allergen effects by binding to ENMs is highly relevant with respect to work place and consumer safety. Therefore, the aim of this present study was to gain an insight into the interactions of gold nanoparticles with different seasonally and perennially occurring outdoor and indoor allergens. Methods: Gold nanoparticles (AuNPs) were conjugated with the major allergens of birch pollen (Bet v 1), timothy grass pollen (Phl p 5) and house dust mite (Der p 1). The AuNP-allergen conjugates were characterized by means of TEM negative staining, dynamic light scattering (DLS), z-potential measurements and hyperspectral imaging. Furthermore, 3D models were constructed, based on the characterization data, to visualize the interaction between the allergens and the AuNPs surface. Differences in the activation of human basophil cells derived from birch/grass pollen- and house dust mite-allergic patients in response to free allergen and AuNP-allergen conjugates were determined using the basophil activation assay (BAT). Potential allergen corona replacement during BAT was controlled for using Western blotting. The protease activity of AuNP-Der p 1 conjugates compared to free Der p 1 was assessed, by an enzymatic activity assay and a cellular assay pertaining to lung type II alveolar epithelial cell tight junction integrity. Results: The formation of a stable corona was found for all three allergens used. Our data suggest, that depending on the allergen, different effects are observed after binding to ENMs, including enhanced allergic responses against Der p 1 and also, for some patients, against Bet v 1. Moreover elevated protease activity of AuNP-Der p 1 conjugates compared to free Der p 1 was found. Conclusion: In summary, this study presents that conjugation of allergens to ENMs can modulate the human allergic response, and that protease activity can be increased. [ABSTRACT FROM AUTHOR]

Published
2016
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