The casein peptide Asn-Pro-Trp-Asp-Gln enforces the intestinal tight junction partly by increasing occludin expression in Caco-2 cells

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We have demonstrated previously that Asn-Pro-Trp-Asp-Gln (NPWDQ, amino acids 107-111 of alpha s(2)-casein) inhibited allergen permeation, such as that demonstrated by ovalbumin, using Caco-2 cells as an in vitro human intestinal epithelial model and in mouse jejunal and ileal loops ex vivo. In the present study, the mechanism underlying this inhibitory activity was examined in Caco-2 cells. Transepithelial resistance value increased in response to the addition of increasing NPWDQ concentrations (10(-6)-10(-4) M), which suggests that this peptide enhanced epithelial barrier function. Next, changes in mRNA expression by the addition of NPWDQ (10(-6) M) were analysed in Caco-2 cells using the microarray method. NPWDQ up-regulated the expression of the occludin gene in cells, but the level of the genes of the claudin family and zonula occludens-1 (ZO-1) was unchanged. Increased protein expression of occludin, but not of claudin-1 or of ZO-1, was also observed. Therefore, it is suggested that NPWDQ up-regulated the expression of occludin in particular and enforced the tight junction barrier. These data imply that a food-derived peptide can fine-tune the epithelial barrier.