Food-derived bioactive peptide lunasin exerts an immunomodulatory role in the healthy human intestinal mucosa

Abstract

[Introduction] The gastrointestinal mucosa represents the main interface between dietary components and the organism. Lunasin is a 43-amino acid peptide naturally present in soybean protein with a variety of biological functions demonstrated by in vitro assays, cell cultures and animal models. Nevertheless, its physiological relevance in human primary intestinal cells has been scarcely investigated.

[Aims and Methods]: Our aim, therefore, was to evaluate the ex vivo biological activity of peptide lunasin in the healthy human intestinal mucosa. Peptide was obtained by chemical synthesis. Colonic biopsies from healthy controls were conditioned with peptide lunasin (5, 50, and 200 mM), both in the presence and absence of pro-inflammatory lipopolysaccharide (LPS). The cytokine milieu (IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, and IL-33) was subsequently assessed on the culture supernatants following overnight culture. The stability and/or modification of peptide during culture was evaluated by liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS).

[Results] Peptide lunasin exerted immunomodulatory effects on the human intestinal mucosa determined by changes on the global cytokine milieu. While lunasin 5 mM was not biologically active, it regulated the cytokine profile at 50 mM expanding the production of IL-10 and IL-33 by intestinal mucosa. Moreover, at higher doses (lunasin 200 μM), this peptide lowered the production of IFN-γ, IL-6 and MCP-1, as well as enhanced an innate immune response characterized by induction of intestinal IL-1β and TNF-α cytokines. Nevertheless, this peptide did not modulate the global cytokine profile when intestinal mucosa was exposed to LPS. The response of colonic biopsies towards the conditioning with peptide lunasin was monitored by HPLC-MS/MS, confirming its presence during cultures.

[Conclusion] Bioactive food peptides may exert physiological effects related to digestive health given their direct and continuous contact with immune mucosa. Peptide lunasin modulated in resting conditions the immune cytokine profile of the healthy intestinal mucosa. This peptide might represent, therefore, a novel agent as functional compound for the prevention of immune and inflammatory- mediated intestinal disorders.