Cephalexin inhibits N-formylated peptide transport and intestinal hyperpermeability in Caco2 cells.

نویسندگان

  • David R Foster
  • Xiaomei Zheng
چکیده

PURPOSE Intestinal barrier integrity is diminished in critical illness and inflammatory bowel disease. Bacterial-derived N-formylated peptides, absorbed by the intestinal oligopeptide transporter, hPEPT1, are involved in the pathogenesis of disease-induced intestinal barrier dysfunction, via stimulation of polymorphonuclear leukocyte (PMN) migration. The purpose of this study was to determine if the hPEPT1 substrate, cephalexin, inhibits the absorption of the N-formylated peptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine ("fMLP"), thereby preventing hyperpermeability in Caco2 cells. METHODS Caco2 monolayers were grown on permeable supports. fMLP (0.1 microM) was added to apical chambers with and without cephalexin (5 and 10 mM), and fMLP effective permeability was calculated. To determine the ability of cephalexin to attenuate intestinal dysfunction, Caco2 cells were co-cultured with human PMN's in the presence of fMLP, cephalexin, and inflammatory cytokines. Monolayer integrity was assessed by measuring mannitol permeability. RESULTS Cephalexin 10 mM significantly reduced fMLP permeability (p=0.007). Monolayer integrity (as indicated mannitol permeability) was decreased in cultures treated with inflammatory cytokines and fMLP, an effect that was attenuated by cephalexin (p<0.01). CONCLUSION Cephalexin inhibits fMLP transport across cultured intestinal monolayers, and partially attenuates PMN-induced intestinal hyperpermeability. The use of pharmacologic hPEPT1 substrates may represent a novel means of preserving intestinal barrier integrity.

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عنوان ژورنال:
  • Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques

دوره 10 3  شماره 

صفحات  -

تاریخ انتشار 2007