A Peptide Derived from Bovine β-Casein Modulates Functional Properties of Bone Marrow-Derived Macrophages from Germfree and Human Flora-Associated Mice

Abstract

The purpose of this study was to evaluate the immunomodulatory activity of a peptide derived from bovine beta-casein (beta-CN), the beta-CN (193-209) peptide, on mouse macrophages that were obtained either from germfree (GF) or from human flora-associated (HF) mice. Macrophages were derived from bone marrow (BMDM) in the presence of recombinant macrophage colony-stimulating factor and exposed to the peptide or lipopolysaccharide (LPS). Membrane marker expression [F4/80, Mac-1, major histocompatibility complex (MHC) class II antigens] and phagocytic activity were assessed by flow cytometry. Production of tumor necrosis factor-alpha and interleukin (IL)-6 was measured by bioassays and production of IL-1alpha, IL-1beta and IL-12 by ELISA. The expression of cytokine mRNA was determined using semi-quantitative reverse transcription-polymerase chain reaction. The beta-CN (193-209) peptide up-regulated MHC class II antigen expression and phagocytic activity of BMDM from GF and HF mice. Its enhancing effect on phagocytosis was greater than that after LPS stimulation (P < 0.01). The peptide induced notable levels of cytokine mRNA in BMDM from GF and HF mice, but it was a significantly weaker inducer of cytokine secretion than LPS. Nevertheless, although flora implantation had no stimulatory influence on basal MHC class II and basal cytokine levels, cells from HF mice were more susceptible than those from GF mice to the peptide effects on these variables. These results indicate that the beta-CN (193-209) peptide could enhance antimicrobial activity of macrophages without proinflammatory effects.

Caseins as source of bioactive peptides

“…However, the Arg residue at the N-or C-terminal region of a peptide Recio and Visser (1999) b (bovine) 193-209 YQEPVLGPVRGPFPIIV Sandre et al (2001) has been suggested to be the leading motif recognizable by specific surface membrane receptors; in this context, it is worth noting that the immunomodulatory ACEinhibitor peptide b-casokinin-10 (among other ACEinhibitory peptides) has Arg in its C-terminus. Opioid peptides are also thought to affect the immunoreactivity of lymphocytes via opiate m-receptors, which, for endorphins, are present on T-lymphocytes and human phagocytic leucocytes (Meisel, 1998).…”

“…The immunomodulatory peptide derived from bovine b-casein, viz. f193-209, was shown to enhance the antimicrobial activity of mouse macrophages, which had been obtained either from germ-free or from human floraassociated mice, without proinflammatory effects (Sandre et al, 2001).…”

The (193–209) 17‐residues peptide of bovine β‐casein is transported through Caco‐2 monolayer

“…This peptide displays immunomodulatory properties and shows mitogenic activity on primed lymph node cells and unprimed rat spleen cells [9]. It manifests chemotactic activity on L14 lymphoblastoid cell line [10], and enhances phagocytosis in rat macrophages [11,12].…”

Isolation and characterisation of a novel antibacterial peptide from bovine αS1-casein

“…In addition, it has been known for some time that milk contains proteins that are biologically active or possess bioactive peptides encrypted within their primary sequence that can be released upon hydrolysis (Clare & Swaisgood, 2000;Schanbacher, Talhouk, & Murray, 1997). The bioactive proteins and peptides derived from milk have been reported to modulate functions of the gastrointestinal tract including an increased gastrointestinal transit time, antidiarrhoeal activity by enhancing water and electrolyte adsorption, vasoregulatory responses, providing nonimmune disease defense and control of microbial infection (Aniansson, Andersson, Lindstedt, & Svanborg, 1990;Clare & Swaisgood, 2000;Daniel, Vohwinkel, & Rehner, 1990;Meisel & Schlimme, 1990;Stromqvist et al, 1995;Schanbacher et al, 1997;Sandre et al, 2001;Silva & Malcata, 2005).…”