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The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation
Translocation of bacteria, primarily Gram-negative pathogenic flora, from the intestinal lumen into the circulatory system leads to sepsis. In newborns, and especially very low birth weight infants, sepsis is a major cause of morbidity and mortality. The results of recently conducted clinical trials...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116316/ https://www.ncbi.nlm.nih.gov/pubmed/27757565 http://dx.doi.org/10.1007/s10534-016-9973-x |
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author | Majka, Grzegorz Więcek, Grażyna Śróttek, Małgorzata Śpiewak, Klaudyna Brindell, Małgorzata Koziel, Joanna Marcinkiewicz, Janusz Strus, Magdalena |
author_facet | Majka, Grzegorz Więcek, Grażyna Śróttek, Małgorzata Śpiewak, Klaudyna Brindell, Małgorzata Koziel, Joanna Marcinkiewicz, Janusz Strus, Magdalena |
author_sort | Majka, Grzegorz |
collection | PubMed |
description | Translocation of bacteria, primarily Gram-negative pathogenic flora, from the intestinal lumen into the circulatory system leads to sepsis. In newborns, and especially very low birth weight infants, sepsis is a major cause of morbidity and mortality. The results of recently conducted clinical trials suggest that lactoferrin, an iron-binding protein that is abundant in mammalian colostrum and milk, may be an effective agent in preventing sepsis in newborns. However, despite numerous basic studies on lactoferrin, very little is known about how metal saturation of this protein affects a host’s health. Therefore, the main objective of this study was to elucidate how iron-depleted, iron-saturated, and manganese-saturated forms of lactoferrin regulate intestinal barrier function via interactions with epithelial cells and macrophages. For these studies, a human intestinal epithelial cell line, Caco-2, was used. In this model, none of the tested lactoferrin forms induced higher levels of apoptosis or necrosis. There was also no change in the production of tight junction proteins regardless of lactoferrin metal saturation status. None of the tested forms induced a pro-inflammatory response in Caco-2 cells or in macrophages either. However, the various lactoferrin forms did effectively inhibit the pro-inflammatory response in macrophages that were activated with lipopolysaccharide with the most potent effect observed for apolactoferrin. Lactoferrin that was not bound to its cognate receptor was able to bind and neutralize lipopolysaccharide. Lactoferrin was also able to neutralize microbial-derived antigens, thereby potentially reducing their pro-inflammatory effect. Therefore, we hypothesize that lactoferrin supplementation is a relevant strategy for preventing sepsis. |
format | Online Article Text |
id | pubmed-5116316 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-51163162016-12-02 The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation Majka, Grzegorz Więcek, Grażyna Śróttek, Małgorzata Śpiewak, Klaudyna Brindell, Małgorzata Koziel, Joanna Marcinkiewicz, Janusz Strus, Magdalena Biometals Article Translocation of bacteria, primarily Gram-negative pathogenic flora, from the intestinal lumen into the circulatory system leads to sepsis. In newborns, and especially very low birth weight infants, sepsis is a major cause of morbidity and mortality. The results of recently conducted clinical trials suggest that lactoferrin, an iron-binding protein that is abundant in mammalian colostrum and milk, may be an effective agent in preventing sepsis in newborns. However, despite numerous basic studies on lactoferrin, very little is known about how metal saturation of this protein affects a host’s health. Therefore, the main objective of this study was to elucidate how iron-depleted, iron-saturated, and manganese-saturated forms of lactoferrin regulate intestinal barrier function via interactions with epithelial cells and macrophages. For these studies, a human intestinal epithelial cell line, Caco-2, was used. In this model, none of the tested lactoferrin forms induced higher levels of apoptosis or necrosis. There was also no change in the production of tight junction proteins regardless of lactoferrin metal saturation status. None of the tested forms induced a pro-inflammatory response in Caco-2 cells or in macrophages either. However, the various lactoferrin forms did effectively inhibit the pro-inflammatory response in macrophages that were activated with lipopolysaccharide with the most potent effect observed for apolactoferrin. Lactoferrin that was not bound to its cognate receptor was able to bind and neutralize lipopolysaccharide. Lactoferrin was also able to neutralize microbial-derived antigens, thereby potentially reducing their pro-inflammatory effect. Therefore, we hypothesize that lactoferrin supplementation is a relevant strategy for preventing sepsis. Springer Netherlands 2016-10-18 2016 /pmc/articles/PMC5116316/ /pubmed/27757565 http://dx.doi.org/10.1007/s10534-016-9973-x Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Article Majka, Grzegorz Więcek, Grażyna Śróttek, Małgorzata Śpiewak, Klaudyna Brindell, Małgorzata Koziel, Joanna Marcinkiewicz, Janusz Strus, Magdalena The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation |
title | The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation |
title_full | The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation |
title_fullStr | The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation |
title_full_unstemmed | The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation |
title_short | The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation |
title_sort | impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116316/ https://www.ncbi.nlm.nih.gov/pubmed/27757565 http://dx.doi.org/10.1007/s10534-016-9973-x |
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