application) Crypt abscesses represent a characteristic finding in acute intestinal inflammation and are thought to contribute to the epithelial dysfunction characterizing such disorders. The hallmark of this histological entity is transepithelial migration of neutrophils across the polarized intestinal monolayer. We have previously shown that one key epithelial transporter (hPepT 1) transports the bacteria-derived chemotactic peptide fMLP and appears to be important for epithelial-neutrophil interactions. The general aim of this proposal is to better understand expression of the intestinal epithelial transporter hPepT1 and its consequences for neutrophil-epithelial interactions. Specifically this proposal has five major aims.
Aims 1 and 2 explore the hypothesis that active inflammation leads to the expression of di/tripeptide transporter hPepT1 in the colon.
Aims 3 and 4 investigate the hypothesis that fMLP uptake by intestinal epithelial cell induces an inflammatory cellular response.
Aim 5 study the hypothesis that the colonic expression of hPepT1 in mice will either induce spontaneous colitis or modify patterns of active inflammation during induced colitis. The project will involve a variety of biochemical methods with emphasis on molecular approaches. The completion of this proposal should molecularly define a link between an active transport process and intestinal inflammation.
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