Effects of lactoferrin on intestinal epithelial cell growth and differentiation: an in vivo and in vitro study

Abstract

This study was designed to analyse the effects of human (h) and bovine lactoferrin (bLF) on the growth and differentiation of intestinal cells using the mice model supplemented with Lactoferrin (LF) and the enterocyte-like model of Caco-2 cells which spontaneously differentiate after confluency. In mice, bLF supplementation increased jejunal villus height and the expression of several intestinal brush border membrane enzymes activities. Addition of bLF or hLF to undifferentiated Caco-2 cells was able to increase cell proliferation with confluency being reached more rapidly. Moreover, when Caco-2 cells were grown in the presence of LF for 3 weeks, brush-border membrane-associated enzyme activities i.e. sucrase, alkaline phosphatase and neutral aminopeptidase, as well as the L-glutamate transporter expression were all increased indicating an increased Caco-2 cell differentiation. Accordingly, cDNA Atlas array and Western blot analysis of cell cycle proteins shown a decreased expression of Cdck2 and an increased TAF1 expression; these proteins being implicated in the regulation of numerous genes related to cellular proliferation and differentiation. These modifications were associated with an inhibition of Caco-2 cell spontaneous apoptosis. Altogether, our results indicate that LF increase in vivo and in vitro enterocyte differentiation. In addition, LF was found to increase in vitro enterocyte proliferation resulting in higher cell density in cell flasks, an effect that was likely partly due to a reduction of the cellular apoptosis. The different stimulation patterns observed for the different parameters associated with cell differentiation in relationship with specific gene regulation is discussed.

Use of a Collagen Membrane to Enhance the Survival of Primary Intestinal Epithelial Cells

“…In view of the viability of attached cells to the ordered collagen membrane, the transcript expression of markers associated with IECs by qRT‐PCR was examined (Blais et al, ). At 8 DOC we found that cultured primary and frozen/thawed cells maintained a significant expression of maltase and alkaline phosphatase (Fig.…”

Comparison of Proliferative Effect of Human Lactoferrin and Its Proteolytic Peptide on Normal and Transformed Epithelial Cells

“…Therefore, the effect of hLF on cellular proliferation is controversial. The reason for the conflicting effect of hLF is not clear, but the effect of hLF on the cell growth appeared to be dependent on the cell types, doses used to test, and both the endogenous and exogenous co-stimulating or co-inhibiting factors in the cells and culture medium [24]. Additionally, the preparation method and the status of hLF could be another possible reason [35].…”

“…Moreover, LF showed a growth-inhibitory effect on some cell types [20][21][22][23]. Therefore, the inconsistent effects of LF on cell growth presumably depend on cell types, the doses used, and possibly the presence of co-growth-promoting or co-growth-inhibiting factors or signals [11,24].…”

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

“…These health benefits include a variety of LF protective effects, ranging from antimicrobial and anti‐inflammatory properties to stimulation of proliferation and differentiation (reviewed in Ref. ) and antiapoptotic effects . However, little is known about the extent to which these properties of LF contribute to stabilization of intestinal epithelial barrier function.…”