title: The tripeptide KdPT protects from intestinal inflammation and maintains intestinal barrier function.
abstract: Treatment options for inflammatory bowel disease (IBD) are incompletely helpful, and surgery is often needed. One promising class of future therapeutic agents for IBD is melanocortin-related peptides, which exhibit potent immunomodulatory effects. We investigated KdPT, a tripeptide derivative of the C-terminus of α-melanocyte-stimulating hormone, as an anti-inflammatory small molecule in vivo and in vitro. Intestinal inflammation was studied after oral administration of dextran sodium sulfate and in IL-10 gene-deficient mice. The effects of KdPT on key colonic epithelial cell functions were studied in vitro and in vivo by evaluating proliferation, wound healing, transepithelial resistance, and expression of tight junction proteins. Melanin assays were performed to determine the melanotropic effects of KdPT. KdPT-treated animals showed markedly reduced severity of inflammation in both colitis models. In colonic epithelial cells, KdPT increased proliferation, accelerated closure of wounds, and improved transepithelial electrical resistance after stimulation with interferon-γ/tumor necrosis factor-α. Moreover, treatment with KdPT also prevented the loss of tight junction protein expression and improved barrier function in vivo. KdPT acted independently of IL-1 receptor type I in vivo and did not affect melanogenesis in vitro. KdPT is capable of attenuating the course of experimental colitis in different models and maintains epithelial cell function. Furthermore, KdPT does not induce pigmentation, emphasizing the potential of this small molecule for the future treatment of IBD.
authors: Department of Medicine B, University of Münster, Münster, Germany.
authors: Dominik
authors: D
authors: Bettenworth
authors: Marion
authors: M
authors: Buyse
authors: Markus
authors: M
authors: Böhm
authors: Rudolf
authors: R
authors: Mennigen
authors: Isabel
authors: I
authors: Czorniak
authors: Klaus
authors: K
authors: Kannengiesser
authors: Thomas
authors: T
authors: Brzoska
authors: Thomas A
authors: TA
authors: Luger
authors: Torsten
authors: T
authors: Kucharzik
authors: Wolfram
authors: W
authors: Domschke
authors: Christian
authors: C
authors: Maaser
authors: Andreas
authors: A
authors: Lügering
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D002478:Cells, Cultured; D003092:Colitis / Q000378:metabolism / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004847:Epithelial Cells; D005455:Fluorescent Antibody Technique; D016753:Interleukin-10 / Q000172:deficiency; D053583:Interleukin-1beta / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000008:administration & dosage*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; C568397:KdPT tripeptide; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D009842:Oligopeptides; D016753:Interleukin-10