Colonic epithelial hPepT1 expression occurs in inflammatory bowel disease:Transport of bacterial peptides influences expression of MHC class 1 molecules

(Background & Aims) under bar: hPepT1 is an intestinal epithelial apical me mbrane transporter responsible for uptake of di/tripeptides (including bact erial derived proinflammatory n-formyl peptides), hPepT1 expression normall y has a strict axial gradient-highest in the proximal small intestine with no expression in the colon. (Methods) under bar: Small intestinal-like cell s (Caco2-BBE), and colonic-like cells (HT29-Cl.19A), and colonic mucosa fro m diseased and control patients were used in the present study. (Results) u nder bar: hPepT1 expression occurs aberrantly in the colon with chronic ulc erative colitis (6 patients) and Crohn's disease (4 patients), but not in n ormal colon (4 patients) or colon with microscopic colitis (4 patients). To model expression of hPepT1 by colonic-like cells in inflamed states, we st ably transfected HT29-Cl.19A cells with a modified hPepT1 tagged on the N-t erminus with green fluorescence protein. Analysis of transfected cells reve aled that: GFP-hPepT1 protein, like the natural protein. is targeted to the apical plasma membrane. In addition, the tagged protein retains the capabi lity of di/tripeptide absorption, and the expression of the tagged protein by HT29-Cl.19A cells permits absorption of N-formyl-methionyl-leucyl-phenyl alanine (fMLP), as occurs in hPepT1 expressing Caco2-BBE cells. fMLP uptake by colonic cells expressing GFP-hPepT1 specifically enhances major histoco mpatibility complex class I surface expression. (Conclusions) under bar: Th ese data collectively indicate that, in some states of chronic inflammation , hPepT1 may be anomolously expressed in the colon. Further, transport of f MLP by hPepT1 potentially stimulates expression of key accessory immune mol ecule, MHC-1.