ABSTRACT
In this study, we examined the therapeutic effects of an immune-stimulating peptide, WKYMVm, in ulcerative colitis. The administration of WKYMVm to dextran sodium sulfate (DSS)-treated mice reversed decreases in body weight, bleeding score and stool score in addition to reversing DSS-induced mucosa destruction and shortened colon. The WKYMVm-induced therapeutic effect against ulcerative colitis was strongly inhibited by a formyl peptide receptor (FPR) 2 antagonist, WRWWWW, indicating the crucial role of FPR2 in this effect. Mechanistically, WKYMVm effectively decreases intestinal permeability by stimulating colon epithelial cell proliferation. WKYMVm also strongly decreases interleukin-23 and transforming growth factor-beta production in the colon of DSS-treated mice. We suggest that the potent immune-modulating peptide WKYMVm and its receptor FPR2 may be useful in the development of efficient therapeutic agents against chronic intestinal inflammatory diseases.
Subject(s)
Animals , Humans , Mice , Adjuvants, Immunologic/pharmacology , Caco-2 Cells , Cell Proliferation , Colitis, Ulcerative/drug therapy , Colon/pathology , Interleukin-23/genetics , Intestinal Mucosa/drug effects , Mice, Inbred C57BL , Oligopeptides/pharmacology , Permeability , Receptors, Formyl Peptide/antagonists & inhibitors , Transforming Growth Factor beta/geneticsABSTRACT
PURPOSE: To evaluate the function of Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm) in human neonatal monocytes. METHODS: The peptide, Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), was synthesized, purified, and prepared in the Peptide Library Support Facility at Pohang University of Science and Technology. Female Sprague-Dawley rats (200+/-10 g) were preinfected with S. aureus and treated with WKYMVm through femoral vein. At various time points, blood samples were obtained by puncture of femoral artery and the serum was plated on the nutrient agar plate. The number of viable bacteria was determined by counting the number of bacterial colonies. In addition, using S. aureus and C. albicans, we evaluated the bactericidal and fungicidal activities of neonatal monocytes, which were separated from umbilical cord blood by Ficoll gradient. RESULTS: The numbers of bacteria in the blood of WKYMVm-treated rats were rapidly decreased with time, as compared with those of the untreated rats. The peptide treatment enhanced the bactericidal activity in vivo within 10 minutes. In neonatal monocytes, WKYMVm stimulated the intracellular killing of S. aureus in a dose dependent manner, showing the maximum effect at 100 nM. WKYMVm stimulated the phagocytic and fungicidal activities against C. albicans in a dose dependent manner, with the maximum effect at the 100 nM. CONCLUSION: These results suggest that WKYMVm may be an effective agent against the neonatal infections.