PepT1-Mediated Tripeptide KPV Uptake Reduces Intestinal Inflammation
Dalmasso G, Charrier-Hisamuddin L, Nguyen HTT, et al. (2008). Gastroenterology.
Summary
Asked how KPV, a three-amino-acid fragment of alpha-MSH, reaches the inside of cells and whether that explains its anti-inflammatory effect. In human intestinal epithelial and T cell lines stimulated with inflammatory cytokines, KPV at nanomolar concentrations reduced NF-kB and MAP kinase signalling and lowered pro-inflammatory cytokine output; uptake experiments indicated the peptide enters through PepT1, a di- and tripeptide transporter expressed in the small intestine and induced in the colon during inflammatory bowel disease. In mice, KPV given in drinking water reduced the severity of chemically induced colitis measured by tissue damage and cytokine expression. Cell and mouse work only; the authors describe KPV as a possible therapeutic candidate rather than a treatment.