title: Whey protein hydrolysates decrease IL-8 secretion in lipopolysaccharide (LPS)-stimulated respiratory epithelial cells by affecting LPS binding to Toll-like receptor 4.
abstract: Whey proteins (WP) exert anti-inflammatory and antioxidant effects. Hyperbaric pressurisation of whey increases its digestibility and changes the spectrum of peptides released during digestion. We have shown that dietary supplementation with pressurised whey improves nutritional status and systemic inflammation in patients with cystic fibrosis (CF). Both clinical indices are largely affected by airway processes, to which respiratory epithelial cells actively contribute. Here, we tested whether peptides released from the digestion of pressurised whey can attenuate the inflammatory responses of CF respiratory epithelial cells. Hydrolysates of pressurised WP (pWP) and native WP (nWP, control) were generated in vitro and tested for anti-inflammatory properties judged by the suppression of IL-8 production in CF and non-CF respiratory epithelial cell lines (CFTE29o- and 1HAEo-, respectively). We observed that, in both cell lines, pWP hydrolysate suppressed IL-8 production stimulated by lipopolysaccharide (LPS) to a greater magnitude compared with nWP hydrolysate. Neither hydrolysate suppressed IL-8 production induced by TNF-α or IL-1β, suggesting an effect on the Toll-like receptor (TLR) 4 pathway, the cellular sensor for LPS. Further, neither hydrolysate affected TLR4 expression or neutralised LPS. Both pWP and nWP hydrolysates similarly reduced LPS binding to surface TLR4, while pWP tended to more potently increase extracellular antioxidant capacity.
  
  
  CONCLUSIONS
  (1) anti-inflammatory properties of whey are enhanced by pressurisation; (2) suppression of IL-8 production may contribute to the clinical effects of pressurised whey supplementation on CF; (3) this effect may be partly explained by a combination of reduced LPS binding to TLR4 and enhanced extracellular antioxidant capacity.
authors.affiliation: School of Dietetics and Human Nutrition, Macdonald Campus of McGill University, Sainte Anne de Bellevue, QC, Canada H9X 3V9.
authors.forename: Michèle M
authors.initials: MM
authors.lastname: Iskandar
authors.forename: Nurlan
authors.initials: N
authors.lastname: Dauletbaev
authors.forename: Stan
authors.initials: S
authors.lastname: Kubow
authors.forename: Nadir
authors.initials: N
authors.lastname: Mawji
authors.forename: Larry C
authors.initials: LC
authors.lastname: Lands
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D003550:Cystic Fibrosis / Q000150:complications / Q000178:diet therapy* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000178:diet therapy* / Q000378:metabolism; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008894:Milk Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D011312:Pressure; D011485:Protein Binding / Q000187:drug effects; D011492:Protein Hydrolysates / Q000494:pharmacology / Q000627:therapeutic use*; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D000067816:Whey Proteins
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016209:Interleukin-8; D008894:Milk Proteins; D010455:Peptides; D011492:Protein Hydrolysates; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D000067816:Whey Proteins