Lactoferrin protects against intestinal inflammation and bacteria‐induced barrier dysfunction in vitro

Annals of the New York Academy of SciencesVolume 1405, Issue 1 p. 177-188 ORIGINAL ARTICLE Lactoferrin protects against intestinal inflammation and bacteria-induced barrier dysfunction in vitro Nina A. Hering, Corresponding Author Nina A. Hering nina.hering@charite.de Department of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Berlin, GermanyAddress for correspondence: Dr. Nina A. Hering, Department of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany. nina.hering@charite.deSearch for more papers by this authorJulia Luettig, Julia Luettig Institute of Clinical Physiology, Department of Gastroenterology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Berlin, GermanySearch for more papers by this authorSusanne M. Krug, Susanne M. Krug Institute of Clinical Physiology, Department of Gastroenterology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Berlin, GermanySearch for more papers by this authorStephanie Wiegand, Stephanie Wiegand Institute of Clinical Physiology, Department of Gastroenterology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Berlin, GermanySearch for more papers by this authorGabriele Gross, Gabriele Gross Mead Johnson Pediatric Nutrition Institute, Nijmegen, the NetherlandsSearch for more papers by this authorEric A. van Tol, Eric A. van Tol Mead Johnson Pediatric Nutrition Institute, Nijmegen, the NetherlandsSearch for more papers by this authorJörg D. Schulzke, Jörg D. Schulzke Institute of Clinical Physiology, Department of Gastroenterology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Berlin, Germany These authors contributed equally to this work.Search for more papers by this authorRita Rosenthal, Rita Rosenthal Institute of Clinical Physiology, Department of Gastroenterology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Berlin, Germany These authors contributed equally to this work.Search for more papers by this author Nina A. Hering, Corresponding Author Nina A. Hering nina.hering@charite.de Department of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Berlin, GermanyAddress for correspondence: Dr. Nina A. Hering, Department of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany. nina.hering@charite.deSearch for more papers by this authorJulia Luettig, Julia Luettig Institute of Clinical Physiology, Department of Gastroenterology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Berlin, GermanySearch for more papers by this authorSusanne M. Krug, Susanne M. Krug Institute of Clinical Physiology, Department of Gastroenterology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Berlin, GermanySearch for more papers by this authorStephanie Wiegand, Stephanie Wiegand Institute of Clinical Physiology, Department of Gastroenterology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Berlin, GermanySearch for more papers by this authorGabriele Gross, Gabriele Gross Mead Johnson Pediatric Nutrition Institute, Nijmegen, the NetherlandsSearch for more papers by this authorEric A. van Tol, Eric A. van Tol Mead Johnson Pediatric Nutrition Institute, Nijmegen, the NetherlandsSearch for more papers by this authorJörg D. Schulzke, Jörg D. Schulzke Institute of Clinical Physiology, Department of Gastroenterology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Berlin, Germany These authors contributed equally to this work.Search for more papers by this authorRita Rosenthal, Rita Rosenthal Institute of Clinical Physiology, Department of Gastroenterology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Berlin, Germany These authors contributed equally to this work.Search for more papers by this author First published: 14 June 2017 https://doi.org/10.1111/nyas.13405Citations: 49 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract The iron-binding glycoprotein lactoferrin (LF) is naturally present in human breast milk. Several studies suggest that LF contributes to infant health and development owing to a variety of protective effects, including antimicrobial and anti-inflammatory features. Therefore, we aimed to elucidate its protective properties on intestinal epithelial barrier dysfunction induced by infection or inflammation using the human epithelial cell culture models HT-29/B6 and T84. During barrier perturbation induced by the proinflammatory cytokine tumor necrosis factor α (TNF-α), bovine LF restored tight junction (TJ) morphometry and inhibited TNF-α–induced epithelial apoptosis. This resulted in an attenuation of the TNF-α–induced decrease in transepithelial resistance (TER) and increases in permeability of fluorescein and FITC–dextran (4 kDa) and was as effective as the apoptosis inhibitor Q-VD-Oph. The enteropathogenic bacterium Yersinia enterocolitica is a frequent cause of diarrhea in early childhood. This involves focal changes in TJ protein expression and localization. LF diminished the Y. enterocolitica–induced drop in TER in the present in vitro model, which was paralleled by an inhibition of the Yersinia-induced reduction of claudin-8 expression via c-Jun kinase signaling. In conclusion, LF exerts protective effects against inflammation- or infection-induced barrier dysfunction in human intestinal cell lines, supporting its relevance for healthy infant development. Citing Literature Supporting Information Filename Description nyas13405-sup-0001-figureS1-S3.docx69.3 KB Figure S1. TER measurements in HT-29/B6 monolayers at specific time points after treatment with different concentrations of lactoferrin. Figure S2. Effects of lactoferrin on TER after cytokine challenge. Figure S3. Effects of lactoferrin on TER in Campylobacter jejuni infection. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume1405, Issue1Special Issue: Tight Junctions and their Proteins IIOctober 2017Pages 177-188 RelatedInformation