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

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.

Intestinal in vitro and ex vivo Models to Study Host-Microbiome Interactions and Acute Stressors

“…In addition, indole-3-propionic acid (IPA) had positive effects on fructose metabolism (Jennis et al, 2018 ). Additionally, T84 cells have been utilized to study protective effects of Lactoferrin on bacterial-induced barrier dysfunction showing that Lactoferrin maintains tight junction structure during Yersinia enterocolitica infection (Hering et al, 2017 ).…”

Lactoferrin Reverses Methotrexate Driven Epithelial Barrier Defect by Inhibiting TGF-β Mediated Epithelial to Mesenchymal Transition

“…Taken orally, it has been shown that approximately 60-70% of lactoferrin survives gastric hydrolysis 20 to enter the intestine, with likely higher ability to tolerate the stomach in neonates due to lower levels of gastric acidity 21 . Numerous clinical studies indirectly suggest a more generalized capacity of lactoferrin to reinforce the body's epithelial barriers, such as a capacity to decrease incidence of necrotizing enterocolitis (NEC) in premature infants 22 , decrease days and severity of diarrheal illness [23][24][25] , and protect against upper respiratory tract infection 23 . In addition, lactoferrin has demonstrated the capacity to protect from methotrexate induced barrier dysfunction in rats 26 .…”

Milk lactoperoxidase decreases ID1 and ID3 expression in human oral squamous cell carcinoma cell lines

“…Moreover, milk provokes a TGF-β response in gingival fibroblasts 20 . Milk is also a rich source of lactoperoxidase 21 , lactoferrin 22 and osteopontin 23 , all causing cellular responses. These findings have prompted us to determine the reaction of oral squamous cell carcinoma cells to milk using molecular screening approaches.…”