KPV

KPV is the tripeptide Lys-Pro-Val, corresponding to residues 11 to 13 at the C-terminus of alpha-melanocyte-stimulating hormone (alpha-MSH), the tridecapeptide produced from proopiomelanocortin by post-translational processing. Work from the Münster group attributes most of the anti-inflammatory activity described for alpha-MSH in experimental systems to this C-terminal tripeptide. KPV has been characterized as a substrate of PepT1, the di- and tripeptide transporter expressed in intestinal epithelium. A related tripeptide, K(D)PT, corresponding to residues 193 to 195 of interleukin-1 beta, has been discussed alongside it by the same investigators.

KPV in the research literature

In intestinal epithelial cell lines (Caco2-BBE and HT29-Cl.19A) and Jurkat T cells stimulated with pro-inflammatory cytokines, nanomolar KPV inhibited NF-κB and MAP kinase signaling and reduced pro-inflammatory cytokine secretion, and uptake experiments with radiolabeled KPV indicated transport into cells via PepT1. In dextran sodium sulfate and TNBS murine colon-inflammation models, KPV was associated with lower pro-inflammatory cytokine expression, reduced myeloperoxidase activity and fewer histologic inflammatory infiltrates.

Experiments in mice expressing a nonfunctional melanocortin-1 receptor suggested that these responses are at least partly independent of MC1R signaling. Formulation studies have also loaded KPV into hyaluronic acid-functionalized polymeric nanoparticles of about 272 nm, which were internalized by colonic epithelial cells and macrophages.