Pepsin Digest of Gliadin Forms Spontaneously Amyloid-Like Nanostructures Influencing the Expression of Selected Pro-Inflammatory, Chemoattractant, and Apoptotic Genes in Caco-2 Cells: Implications for Gluten-Related Disorders

Herrera MG, Nicoletti F, Gras M, Dörfler P, Tonali NM, Hannappel Y, Ennen I, Hütten A, Hellweg T, Lammers KM:, Dodero VI (2021)
Molecular nutrition & food research.

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Abstract / Bemerkung
SCOPE: Proteolysis-resistant gliadin peptides are intensely investigated in biomedical research related to Celiac Disease and gluten-related disorders. Herein, the first integrated supramolecular investigation of pepsin-digested gliadin peptides, p-gliadin, is presented in combination with its functional behavior in Caco-2 cell line.; METHODS AND RESULTS: First, we investigated gliadin degradation by pepsin at pH 3, and the physicochemical properties of p-gliadin were compared with gliadin. An integrated approach using interfacial, spectroscopic, and microscopic techniques revealed that the p-gliadin forms spontaneously soluble large supramolecular structures, mainly oligomers and fibrils capable of binding amyloid-sensitive dyes. The self-assembly of p-gliadin starts at a concentration of 0.40mug/ml. Second, we stimulated CaCo-2 cells with the p-gliadin supramolecular system and screened the mRNA expression levels of a panel of genes involved in cellular inflammation, apoptosis, permeability, and chemoattraction of immune cells. Our findings suggest that p-gliadin composed of supramolecular structures triggers significant mRNA up-regulation (p <0.05) of pro-apoptotic biomarkers (ratio Bcl2/Bak-1), chemokines (CCL2, CCL3, CCL4, CCL5, CXCL8) and the chemokine receptor CXCR3.; CONCLUSIONS: This work demonstrates that p-gliadin is interfacial active, forming spontaneously amyloid-type structures that trigger genes in the Caco-2 cell line involved in the recruitment of specialized immune cells. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Erscheinungsjahr
2021
Zeitschriftentitel
Molecular nutrition & food research
eISSN
1613-4133
Page URI
https://pub.uni-bielefeld.de/record/2955513

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Herrera MG, Nicoletti F, Gras M, et al. Pepsin Digest of Gliadin Forms Spontaneously Amyloid-Like Nanostructures Influencing the Expression of Selected Pro-Inflammatory, Chemoattractant, and Apoptotic Genes in Caco-2 Cells: Implications for Gluten-Related Disorders. Molecular nutrition & food research. 2021.
Herrera, M. G., Nicoletti, F., Gras, M., Dörfler, P., Tonali, N. M., Hannappel, Y., Ennen, I., et al. (2021). Pepsin Digest of Gliadin Forms Spontaneously Amyloid-Like Nanostructures Influencing the Expression of Selected Pro-Inflammatory, Chemoattractant, and Apoptotic Genes in Caco-2 Cells: Implications for Gluten-Related Disorders. Molecular nutrition & food research. https://doi.org/10.1002/mnfr.202100200
Herrera, M. G., Nicoletti, F., Gras, M., Dörfler, P., Tonali, N. M., Hannappel, Y., Ennen, I., Hütten, A., Hellweg, T., Lammers, K. M. :, et al. (2021). Pepsin Digest of Gliadin Forms Spontaneously Amyloid-Like Nanostructures Influencing the Expression of Selected Pro-Inflammatory, Chemoattractant, and Apoptotic Genes in Caco-2 Cells: Implications for Gluten-Related Disorders. Molecular nutrition & food research.
Herrera, M.G., et al., 2021. Pepsin Digest of Gliadin Forms Spontaneously Amyloid-Like Nanostructures Influencing the Expression of Selected Pro-Inflammatory, Chemoattractant, and Apoptotic Genes in Caco-2 Cells: Implications for Gluten-Related Disorders. Molecular nutrition & food research.
M.G. Herrera, et al., “Pepsin Digest of Gliadin Forms Spontaneously Amyloid-Like Nanostructures Influencing the Expression of Selected Pro-Inflammatory, Chemoattractant, and Apoptotic Genes in Caco-2 Cells: Implications for Gluten-Related Disorders”, Molecular nutrition & food research, 2021.
Herrera, M.G., Nicoletti, F., Gras, M., Dörfler, P., Tonali, N.M., Hannappel, Y., Ennen, I., Hütten, A., Hellweg, T., Lammers, K.M.:, Dodero, V.I.: Pepsin Digest of Gliadin Forms Spontaneously Amyloid-Like Nanostructures Influencing the Expression of Selected Pro-Inflammatory, Chemoattractant, and Apoptotic Genes in Caco-2 Cells: Implications for Gluten-Related Disorders. Molecular nutrition & food research. (2021).
Herrera, María Georgina, Nicoletti, Francesco, Gras, Marion, Dörfler, Philipp, Tonali, Nicolo Michele, Hannappel, Yvonne, Ennen, Inga, Hütten, Andreas, Hellweg, Thomas, Lammers, Karen M:, and Dodero, Veronica Isabel. “Pepsin Digest of Gliadin Forms Spontaneously Amyloid-Like Nanostructures Influencing the Expression of Selected Pro-Inflammatory, Chemoattractant, and Apoptotic Genes in Caco-2 Cells: Implications for Gluten-Related Disorders”. Molecular nutrition & food research (2021).

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