title: Antrum Mucosal Protein-18 Peptide Targets Tight Junctions to Protect and Heal Barrier Structure and Function in Models of Inflammatory Bowel Disease.
abstract: BACKGROUND
  A peptide derived from Antrum Mucosal Protein (AMP)-18 (gastrokine-1) reduces the extent of mucosal erosions and clinical severity in mice with dextran sulfate sodium-induced colonic injury. This study set out to determine if AMP peptide was also therapeutic for immune- and cytokine-mediated mouse models of intestinal injury and inflammatory bowel diseases by enhancing and stabilizing tight junctions.
  
  
  METHODS
  Therapeutic effects of AMP peptide were examined in interleukin-10-deficient and a T-cell adoptive transfer models of colitis in immunodeficient recombinase activating gene-1 knock-out (RAG-1-/-) mice. Mechanisms by which AMP peptide enhances barrier function and structure were studied ex vivo using intestine and colon from mice given lipopolysaccharide and in AMP-18-deficient mice given dextran sulfate sodium.
  
  
  RESULTS
  In interleukin-10-deficient mice given piroxicam, AMP peptide enhanced recovery after weight loss, protected against colon shortening and segmental dilation, and reduced the colitis activity score. In the T-cell transfer model, treatment with the peptide protected against colon shortening. In mice given lipopolysaccharide in vivo to induce gut injury, AMP peptide prevented the onset of, and reversed established intestinal hyperpermeability by targeting TJ proteins and perijunctional actin. AMP-18-deficient mice challenged with dextran sulfate sodium exhibited increased mortality, developed erosions in the colon, and had lower levels of ZO-1 in TJs than heterozygous littermates or wild-type mice.
  
  
  CONCLUSIONS
  The results indicate that AMP-18/peptide may serve a protective role against injury along the gastrointestinal mucosal barrier, and recommend further development of AMP peptide as a novel agent to treat patients with inflammatory bowel disease.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Peili
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Danika
authors.initials: D
authors.lastname: Bakke
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Lauren
authors.initials: L
authors.lastname: Kolodziej
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: James
authors.initials: J
authors.lastname: Lodolce
authors.affiliation: Department of Pathology, University of Chicago, Chicago, Illinois.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Weber
authors.affiliation: Department of Medicine, Indiana University School of Medicine, South Bend, Indiana.
authors.forename: David L
authors.initials: DL
authors.lastname: Boone
authors.affiliation: The University of Chicago, Department of Medicine, MC5100, 5841 South Maryland, Avenue, Chicago, IL.
authors.forename: F Gary
authors.initials: FG
authors.lastname: Toback
mesh_terms: D000199:Actins / Q000378:metabolism; D019264:Adoptive Transfer; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000293:injuries; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D016753:Interleukin-10 / Q000172:deficiency; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D036361:Peptide Hormones / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D010894:Piroxicam; D020011:Protective Agents / Q000494:pharmacology; D012720:Severity of Illness Index; D062725:Tight Junction Proteins / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism*
chemical_list: D000199:Actins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; C477000:GKN1 protein, human; D008070:Lipopolysaccharides; D036361:Peptide Hormones; D020011:Protective Agents; D062725:Tight Junction Proteins; D016753:Interleukin-10; D010894:Piroxicam; D016264:Dextran Sulfate