Sialic acid-containing milk proteins show differential immunomodulatory activities independent of sialic acid.
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.
Mikkelsen
Trine L
TL
BioCentrum-DTU, Biochemistry and Nutrition, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
Bakman
Susanne
S
Sørensen
Esben S
ES
Barkholt
Vibeke
V
Frøkiaer
Hanne
H
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
D002364:Caseins; D016207:Cytokines; D008070:Lipopolysaccharides; D008894:Milk Proteins; D010835:Phytohemagglutinins; D003208:Concanavalin A; D009439:Neuraminidase; D007781:Lactoferrin; D019158:N-Acetylneuraminic Acid