622 Fibroblast function in vitro modulated by the melanocortin tripeptide derivatives KdPT and WOL074-029

We previously reported on the impact of melanocortin peptide alpha-melanocyte-stimulating hormone (alpha-MSH) fibroblast function including skin fibrosis. Truncated peptides from C-terminal domain alpha-MSH as well some derivatives have persevered immunomodulating effects but do not bind to melanocortin-1 receptor (MC-1R). Thus, they elicit MC-1R-mediated pigmentation an obligatory adverse effect MC1R agonistic peptides. Among tripeptide is Lys-Pro-d-Thr (KdPT) which only suppressed interleukin-IL-1beta-mediated expression proinflammatory cytokines also exhibited beneficial in animal models inflammatory bowel disease patients with Crohn’s disease. Here we investigated whether KdPT and another more stable derivative, WOL074-029 are capable suppressing activation induced by transforming growth factor-beta1 (TGF-beta1). Both mRNA collagen I, fibronectin connective tissue factor alpha-smooth muscle actin human dermal fibroblasts (HDF) compared TGF-beta1 alone shown real-time RT-PCR analysis. These were dose-independent detectable at subnanomolar levels both In accordance, secretion I was significantly WOL074-029. The did interfere smad2/3 signalling Western immunoblotting immunofluorescence Interestingly, PepT2 PepT1 present HDF raising possibility that observed these transporters. Future studies progress further define mode action vivo relevance findings.