title: Sialic acid-containing milk proteins show differential immunomodulatory activities independent of sialic acid.
abstract: The immunomodulatory activities of four sialic acid-containing milk proteins (kappa-casein, glycomacropeptide, lactoferrin, and proteose peptone-3 component) were determined, and the role of sialic acid was evaluated. Two in vitro models were used: murine splenocyte proliferation, where the effect on LPS-, Con A-, and PHA-stimulated proliferation was studied, and cytokine production in LPS-stimulated murine dendritic cells (DC). All four proteins inhibited LPS-induced splenocyte proliferation, though to different degrees, and independently of sialic acid. kappa-Casein strongly inhibited PHA-induced proliferation and had a weak inhibitory effect on Con A-induced proliferation, whereas lactoferrin stimulated Con A-induced proliferation. kappa-Casein, glycomacropeptide, and lactoferrin differentially affected cytokine production by DC: kappa-casein significantly inhibited production of TNF-alpha, IL-10, -12, -6, and -1beta, independent of sialic acid, whereas less-marked effects of glycomacropeptide and lactoferrin were seen. These findings thus point to important immunosuppressive effects of some milk proteins and indicate that they may function via different mechanisms.
authors.affiliation: BioCentrum-DTU, Biochemistry and Nutrition, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
authors.forename: Trine L
authors.initials: TL
authors.lastname: Mikkelsen
authors.forename: Susanne
authors.initials: S
authors.lastname: Bakman
authors.forename: Esben S
authors.initials: ES
authors.lastname: Sørensen
authors.forename: Vibeke
authors.initials: V
authors.lastname: Barkholt
authors.forename: Hanne
authors.initials: H
authors.lastname: Frøkiaer
mesh_terms: D000818:Animals; D002364:Caseins / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D007109:Immunity / Q000187:drug effects*; D007781:Lactoferrin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008894:Milk Proteins / Q000737:chemistry* / Q000494:pharmacology*; D019158:N-Acetylneuraminic Acid / Q000032:analysis*; D009439:Neuraminidase / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013329:Structure-Activity Relationship
chemical_list: D002364:Caseins; D016207:Cytokines; D008070:Lipopolysaccharides; D008894:Milk Proteins; D010835:Phytohemagglutinins; D003208:Concanavalin A; D009439:Neuraminidase; D007781:Lactoferrin; D019158:N-Acetylneuraminic Acid