A human β-casein-derived peptide BCCY-1 modulates the innate immune response

•BCCY-1 can penetrate cell membrane of monocytes without obvious cytotoxicity.•BCCY-1 enhanced chemokine production and monocyte migration.•The scrambled version of BCCY-1 has no modulatory effects on monocytes.•BCCY-1 activated the NF-κB and MAPK signaling pathways.•Abundances of peptides containing BCCY-1 fragment were decreased in preterm milk. In this study, we report a novel peptide corresponding to the sequence of human β-casein (named BCCY-1), which was identified in our previous peptidome analysis of human milk and has great immunomodulatory activity. The results revealed that peptide BCCY-1, but not the scrambled version, enhanced monocyte migration without obvious toxicities. This selective effect was mediated via increased production of chemokines by peptide stimulated monocytes. Moreover, BCCY-1 exerted its modulatory effects by activating nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling. The abundances of peptide BCCY-1 and the peptides partially encompassing its fragment were found to be lower in preterm milk than in term milk. Our study may lead to new insights into the immunoregulatory effects of casein-derived peptides and facilitate the discovery of novel peptide-based food and pharmaceutical products.