PMID- 27055186 OWN - NLM STAT- MEDLINE DCOM- 20170522 LR - 20181202 IS - 1530-0447 (Electronic) IS - 0031-3998 (Linking) VI - 80 IP - 2 DP - 2016 Aug TI - Cysteinyl-glycine reduces mucosal proinflammatory cytokine response to fMLP in a parenterally-fed piglet model. PG - 293-8 LID - 10.1038/pr.2016.69 [doi] AB - BACKGROUND: 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. METHODS: 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. RESULTS: PN piglets had lower mucosal IL-10 by approximately 20% (P < 0.01). Cysteinyl-glycine lowered TNF-alpha response to fMLP in PN-fed animals and IFN-gamma response to fMLP in both groups (P < 0.05). The free cysteine and glycine treatment reduced TNF-alpha in sow-fed animals (P < 0.05). fMLP affected villus height in parenterally (P < 0.05), but not sow-fed animals. CONCLUSION: 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. FAU - Nosworthy, Matthew G AU - Nosworthy MG AD - Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland, Canada. FAU - Brunton, Janet A AU - Brunton JA AD - Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland, Canada. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160407 PL - United States TA - Pediatr Res JT - Pediatric research JID - 0100714 RN - 0 (Cytokines) RN - 0 (Dipeptides) RN - 130068-27-8 (Interleukin-10) RN - 384644SZ9T (cysteinylglycine) RN - 3OWL53L36A (Mannitol) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - EC 1.11.1.7 (Peroxidase) RN - K848JZ4886 (Cysteine) RN - TE7660XO1C (Glycine) SB - IM MH - Animals MH - Cysteine/chemistry MH - Cytokines/*metabolism MH - Dipeptides/*chemistry MH - Disease Models, Animal MH - Genetic Predisposition to Disease MH - Glycine/chemistry MH - Inflammation/*metabolism MH - Interleukin-10/metabolism MH - Intestinal Mucosa/metabolism MH - Mannitol/chemistry MH - Mucous Membrane/*metabolism MH - N-Formylmethionine Leucyl-Phenylalanine/*chemistry MH - Parenteral Nutrition MH - Perfusion MH - Peroxidase/metabolism MH - Random Allocation MH - Swine MH - Time Factors EDAT- 2016/04/08 06:00 MHDA- 2017/05/23 06:00 CRDT- 2016/04/08 06:00 PHST- 2015/09/23 00:00 [received] PHST- 2016/02/02 00:00 [accepted] PHST- 2016/04/08 06:00 [entrez] PHST- 2016/04/08 06:00 [pubmed] PHST- 2017/05/23 06:00 [medline] AID - pr201669 [pii] AID - 10.1038/pr.2016.69 [doi] PST - ppublish SO - Pediatr Res. 2016 Aug;80(2):293-8. doi: 10.1038/pr.2016.69. Epub 2016 Apr 7.