PepT1 mediates colon damage by transporting fMLP in rats with bowel resection

Background. The intestinal oligopeptide transporter (PepT1) is responsible for the absorption of nutrient di-tripeptide and mediates the transportation of bacterial product N-formylmethionylleucyl-phenylalanine (fMLP) that induces intestinal inflammation. PepT1 is absent from normal colon epithelia but is abnormally expressed in the colon of patients with inflammatory bowel diseases. This study was designed to investigate the role of PepT1 in colonic inflammation and its relation with fMLP. Materials and methods. PepT1 mRNA expression was analyzed by RT-PCR and oligopeptide transportation was quantified by the luminal perfusion with cephalexin in rats following 80% small bowel resection. The inflammatory effects of PepT1-mediated fMLP transport were also investigated by the measurement of myeloperoxidase (MPO) activity, histological analysis, and the use of Gly-Gly (Glycine-Glycine, a competitive PepT1 blocker). Results. The overexpression of PepT1 was observed, peaking at 2 weeks post-operation, with its levels declining to 12% at week 4. The ability of oligopeptide transport was correlated with the PepT1 levels. The fMLP perfusion into the colon of rats with bowel resection resulted in an increased MPO activity and mucosal inflammation at week 2, but not at week 4 post-operation. The administration of Gly-Gly (50 mm) competitively inhibited PepT1, reducing the fMLP-associated MPO activation and colonic mucosal damage. Conclusions. The colonic PepT1 overexpression induced by bowel resection increases the transport of bacterial product fMLP and hence causes colonic inflammation, which may serve as a previously unrecognized pathway resulting in colon mucosa damage. (c) 2006 Elsevier Inc. All rights reserved.