title: The 5A apolipoprotein A-I (apoA-I) mimetic peptide ameliorates experimental colitis by regulating monocyte infiltration.
abstract: New therapies for inflammatory bowel disease (IBD) are highly desirable. As apolipoprotein (apo)A-I mimetic peptides are beneficial in several animal models of inflammation, we hypothesized that they might be effective at inhibiting murine colitis.
  
  
  
  Daily injections of 5A peptide, a synthetic bihelical apoA-I mimetic dissolved in PBS, or PBS alone were administered to C57BL/6 mice fed 3% (w v(-1) ) dextran sodium sulfate (DSS) in drinking water or healthy controls.
  
  
  
  Daily treatment with 5A peptide potently restricted DSS-induced inflammation, as indicated by improved disease activity indices and colon histology, as well as decreased intestinal tissue myeloperoxidase levels and plasma TNFα and IL-6 concentrations. Additionally, plasma levels of monocyte chemoattractant protein-1 and the monocyte expression of adhesion-mediating molecule CD11b were down-regulated, pro-inflammatory CD11b(+) /Ly6c(high) monocytes were decreased, and the number of intestinal monocytes was reduced in 5A peptide-treated animals as determined by intravital macrophage-related peptide-8/14-directed fluorescence-mediated tomography and post-mortem immunhistochemical F4/80 staining. Intravital fluorescence microscopy of colonic microvasculature demonstrated inhibitory effects of 5A peptide on leukocyte adhesion accompanied by reduced plasma levels of the soluble adhesion molecule sICAM-1. In vitro 5A peptide reduced monocyte adhesion and transmigration in TNFα-stimulated monolayers of human intestinal microvascular endothelial cells. Increased susceptibility to DSS-induced inflammation was noted in apoA-I(-/-) mice.
  
  
  
  The 5A peptide is effective at ameliorating murine colitis by preventing intestinal monocyte infiltration and activation. These findings point to apoA-I mimetics as a potential treatment approach for IBD.
authors.affiliation: Department of Medicine B, University Hospital Münster, Münster, Germany.
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Nowacki
authors.affiliation: National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
authors.affiliation: Department of Medicine B, University Hospital Münster, Münster, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Bettenworth
authors.affiliation: Translational Research Imaging Center, Department of Clinical Radiology, University Hospital Münster, Münster, Germany.
authors.forename: Michel
authors.initials: M
authors.lastname: Eisenblätter
authors.affiliation: Department of General and Visceral Surgery, University Hospital Münster, Münster, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Vowinkel
authors.affiliation: Department of General and Visceral Surgery, University Hospital Münster, Münster, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Becker
authors.affiliation: Institute of Immunology, University Hospital Münster, Münster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogl
authors.affiliation: Institute of Immunology, University Hospital Münster, Münster, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.affiliation: Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, GZ Groningen, The Netherlands.
authors.forename: Uwe J
authors.initials: UJ
authors.lastname: Tietge
authors.affiliation: Medical Care Center Portal 10, Münster, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lügering
authors.affiliation: Department of Medicine B, University Hospital Münster, Münster, Germany.|Department of Gastroenterology, Klinikum Bielefeld, Bielefeld, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Heidemann
authors.affiliation: Center for Laboratory Medicine, University Hospital Münster, Münster, Germany.
authors.forename: Jerzy-Roch
authors.initials: JR
authors.lastname: Nofer
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000172:deficiency / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016264:Dextran Sulfate / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects* / Q000473:pathology
chemical_list: D016632:Apolipoprotein A-I; D016264:Dextran Sulfate