title: Cysteinyl-glycine reduces mucosal proinflammatory cytokine response to fMLP in a parenterally-fed piglet model.
abstract: PepT1 transports dietary and bacterial peptides in the gut. We hypothesized that cysteinyl-glycine would ameliorate the inflammatory effect of a bacterial peptide, formyl-methionyl-leucyl-phenylalanine (fMLP), in both sow-fed and parenterally-fed piglets.
  
  
  
  An intestinal perfusion experiment was performed in piglets (N = 12) that were sow-reared or provided with parenteral nutrition (PN) for 4 d. In each piglet, five segments of isolated intestine were perfused with five treatments including cysteine and glycine, cysteinyl-glycine, fMLP, free cysteine and glycine with fMLP, or cysteinyl-glycine with fMLP. Mucosal cytokine responses and intestinal morphology was assessed in each gut segment.
  
  
  
  PN piglets had lower mucosal IL-10 by approximately 20% (P < 0.01). Cysteinyl-glycine lowered TNF-α response to fMLP in PN-fed animals and IFN-γ response to fMLP in both groups (P < 0.05). The free cysteine and glycine treatment reduced TNF-α in sow-fed animals (P < 0.05). fMLP affected villus height in parenterally (P < 0.05), but not sow-fed animals.
  
  
  
  Parenteral feeding conferred a susceptibility to mucosal damage by fMLP. The dipeptide was more effective at attenuating the inflammatory response to a bacterial peptide than free amino acids. This may be due to competitive inhibition of fMLP transport or a greater efficiency of transport of dipeptides.
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Nosworthy
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Brunton
mesh_terms: D000818:Animals; D003545:Cysteine / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism*; D004151:Dipeptides / Q000737:chemistry*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D005998:Glycine / Q000737:chemistry; D007249:Inflammation / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008353:Mannitol / Q000737:chemistry; D009092:Mucous Membrane / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000737:chemistry*; D010288:Parenteral Nutrition; D010477:Perfusion; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D013552:Swine; D013997:Time Factors
chemical_list: D016207:Cytokines; D004151:Dipeptides; D016753:Interleukin-10; C028505:cysteinylglycine; D008353:Mannitol; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase; D003545:Cysteine; D005998:Glycine