title: Whey protein hydrolysate and branched-chain amino acids downregulate inflammation-related genes in vascular endothelial cells.
abstract: A recent review of clinical studies reports that dairy products may improve inflammation, a key etiologic cardiovascular disease risk factor. Yet the impact of dairy proteins on inflammatory markers is controversial and could be mediated by a differential impact of whey proteins and caseins. In this study, we hypothesized that whey proteins may have a greater anti-inflammatory effect than caseins. A model of human umbilical vein endothelial cells, with or without TNF-α stimulation, was used to investigate the effect of several dairy protein compounds on inflammation. Specifically, the impact of whey proteins either isolate or hydrolysate, caseins, and their amino acids on expression of TNF, VCAM-1, SOD2, and eNOS was examined. After a 24-hour incubation period, whey protein hydrolysate, leucine, isoleucine, and valine attenuated the TNF-α-induced endothelial inflammation by normalizing TNF and eNOS gene expression. This effect was not observed in unstimulated cells. Oppositely, caseins, a whey protein/casein mixture (1:4 w/w), and glutamine aggravated the TNF-α-induced TNF and SOD2 gene expression. Yet caseins and whey protein/casein mixture decreased VCAM-1 expression in both unstimulated and stimulated human umbilical vein endothelial cells. Measurement of TNF-α in cell supernatants by immunoassay substantiates gene expression data without reaching statistical significance. Taken together, this study showed that whey proteins and their major amino acids normalize TNF-α-induced proinflammatory gene expression in endothelial cells.
authors.affiliation: Endocrinology and Nephrology, CHU de Québec Research Center and the Department of Kinesiology, Faculty of Medicine, Université Laval, Québec, Québec, Canada G1V 4G2. Electronic address: marine-da-silva.1@ulaval.ca.
authors.forename: Marine S
authors.initials: MS
authors.lastname: Da Silva
authors.affiliation: Laboratory of Molecular Pharmacology, CHU de Québec Research Center and the Faculty of Pharmacy, Université Laval, Québec, Québec, Canada G1V 4G2. Electronic address: cyril.bigo@crchudequebec.ulaval.ca.
authors.forename: Cyril
authors.initials: C
authors.lastname: Bigo
authors.affiliation: Laboratory of Molecular Pharmacology, CHU de Québec Research Center and the Faculty of Pharmacy, Université Laval, Québec, Québec, Canada G1V 4G2. Electronic address: olivier.barbier@crchudequebec.ulaval.ca.
authors.forename: Olivier
authors.initials: O
authors.lastname: Barbier
authors.affiliation: Endocrinology and Nephrology, CHU de Québec Research Center and the Department of Kinesiology, Faculty of Medicine, Université Laval, Québec, Québec, Canada G1V 4G2. Electronic address: iwona.rudkowska@crchudequebec.ulaval.ca.
authors.forename: Iwona
authors.initials: I
authors.lastname: Rudkowska
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002364:Caseins / Q000494:pharmacology; D003611:Dairy Products; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D005973:Glutamine / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D007532:Isoleucine / Q000494:pharmacology; D007930:Leucine / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011492:Protein Hydrolysates / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014633:Valine / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D000067816:Whey Proteins / Q000494:pharmacology*; D000099156:Superoxide Dismutase 2
chemical_list: D000597:Amino Acids, Branched-Chain; D000893:Anti-Inflammatory Agents; D002364:Caseins; D005973:Glutamine; D007532:Isoleucine; D007930:Leucine; D052250:Nitric Oxide Synthase Type III; D011492:Protein Hydrolysates; D013482:Superoxide Dismutase; D014409:Tumor Necrosis Factor-alpha; D014633:Valine; D019010:Vascular Cell Adhesion Molecule-1; D000067816:Whey Proteins; D000099156:Superoxide Dismutase 2; C496314:NOS3 protein, human
keywords: Branched-chain amino acid; Casein; Endothelial cells; Tumor necrosis factor–alpha; Whey protein