title: Correlation between cyclical epithelial barrier dysfunction and bacterial translocation in the relapses of intestinal inflammation.
abstract: BACKGROUND
  Although several factors have been implicated in the pathogenesis of inflammatory bowel disease (IBD), the mechanisms underlying the recurrent relapses have not yet been clarified. We hypothesized that epithelial barrier dysfunction, associated with intestinal motor disturbances, could play a key role in exacerbation of inflammatory illness due to an increased uptake of luminal antigen and bacterial translocation.
  
  
  METHODS
  Indomethacin administration to rats induced a long-lasting oscillation of active and quiescent phases of inflammation associated with phases of hypo and hypermotility. Rats selected at either active or quiescent phase and from 2 to 60 days after indomethacin treatment were used. Short-circuit current; conductance and HRP flux were evaluated in small intestinal segments mounted in Ussing Chambers. Enterocyte endosomes containing HRP and ultrastructural damage were assessed by electron microscopy. Bacterial translocation was determined by cultures from mesenteric lymph nodes.
  
  
  RESULTS
  Rats with induced enteritis in both phases demonstrated a long-lasting increase of epithelial paracellular permeability. In contrast, transcellular permeability was only disturbed during the active phases, coinciding with bacterial translocation and the increase in inflammatory parameters. Furthermore, although mithochondrial damage was observed throughout the inflammatory state, alterations were worse during the active phase.
  
  
  CONCLUSIONS
  The sustained enhancement of paracellular permeability could facilitate the constant passage of luminal antigens through the mucosa, and hence, be the basis for chronicity. By contrast, transcellular permeability only increases during the active phases, when hypomotility and bacterial translocation are also present, suggesting this factor may play a critical role in the course of acute relapses in IBD.
authors.affiliation: Cell Biology, Physiology and Immunology Department, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Porras
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Martín
authors.forename: Ping-Chang
authors.initials: PC
authors.lastname: Yang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jury
authors.forename: Mary H
authors.initials: MH
authors.lastname: Perdue
authors.forename: Patri
authors.initials: P
authors.lastname: Vergara
mesh_terms: D000818:Animals; D018988:Bacterial Translocation / Q000502:physiology*; D001692:Biological Transport; D004594:Electrophysiology / Q000379:methods; D020895:Enterocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D004848:Epithelium / Q000502:physiology / Q000648:ultrastructure; D018928:Immunity, Mucosal; D007213:Indomethacin / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology*; D007421:Intestine, Small / Q000187:drug effects / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000473:pathology; D009195:Peroxidase / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence
chemical_list: D009195:Peroxidase; D007213:Indomethacin