title: The N-terminal fragment of chromogranin A, vasostatin-1 protects mice from acute or chronic colitis upon oral administration.
abstract: BACKGROUND
  Vasostatin-1 (VS-1), the N-terminal fragment of chromogranin A (CgA), decreases the permeability of endothelial cells in vitro and in vivo.
  
  
  OBJECTIVE
  Here, we investigated whether a similar effect could be observed also on intestinal epithelial cells (IECs) in vitro and whether VS-1 could have favorable effects on animal models of acute or chronic colitis, which are characterized by increased permeability of the intestinal epithelium.
  
  
  METHODS
  In vitro, VS-1 was tested on IEC monolayers showing increased permeability, on mechanically injured IEC monolayers, and on the production of the chemokine IL-8/KC by lipopolysaccharide (LPS)-stimulated IECs. In vivo, VS-1 was tested in animal models of dextran sodium salt (DSS)-induced acute or chronic colitis.
  
  
  RESULTS
  In vitro, VS-1 inhibited increased permeability of IECs induced by interferon-γ and tumor necrosis factor-α. Moreover, VS-1 promoted healing of mechanically injured IEC monolayers, most likely through stimulation of cell migration, rather than cell proliferation. Eventually, VS-1 inhibited LPS-induced production of IL-8. In vivo, VS-1 exerted protective effects in animal models of acute or chronic colitis upon oral, but not systemic administration.
  
  
  CONCLUSIONS
  VS-1 is therapeutically active in animal models of acute or chronic, DSS-induced colitis. The mechanisms underlying this effect are likely to be multiple, and may include inhibition of enhanced intestinal permeability, repair of injured intestinal mucosae, and inhibition of the production of IL-8/KC and possibly other inflammatory cytokines.
authors.affiliation: iMIL-Italian Mucosal Immunity Laboratory, Dipartimento di Morfologia Umana e Scienze Biomediche Città Studi, Università degli Studi di Milano, via Mangiagalli, 31-20133 Milano, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Rumio
authors.forename: Giuseppina F
authors.initials: GF
authors.lastname: Dusio
authors.forename: Barbara
authors.initials: B
authors.lastname: Colombo
authors.forename: Anna
authors.initials: A
authors.lastname: Gasparri
authors.forename: Diego
authors.initials: D
authors.lastname: Cardani
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Marcucci
authors.forename: Angelo
authors.initials: A
authors.lastname: Corti
mesh_terms: D000284:Administration, Oral; D000818:Animals; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D053379:Chromogranin A / Q000008:administration & dosage / Q000493:pharmacokinetics; D002908:Chronic Disease; D003092:Colitis / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics; D020011:Protective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053379:Chromogranin A; D016209:Interleukin-8; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; C064110:vasostatin I; D007371:Interferon-gamma