title: Role of IL-10 in hepatocyte tight junction alteration in mouse model of experimental colitis.
abstract: BACKGROUND
  A variety of hepatobiliary abnormalities have been described in patients with chronic inflammatory bowel diseases (IBDs). The purpose of this study was to investigate the role of endogenous IL-10 in alteration of hepatocyte TJ paracellular barrier and in the rapid transcytotic vesicular pathway modification associated with intestinal inflammation.
  
  
  METHODS
  To address this question, we used an experimental model of colitis, induced by dinitrobenzene sulfonic acid (DNBS). When compared to DNBS-treated IL-10 wild-type (IL-10WT) mice, DNBS-treated IL-10 knock-out mice (IL-10KO) mice experienced a higher rate of the extent and severity of the histological signs of colon injury.
  
  
  RESULTS
  Colon and liver levels of the pro-inflammatory cytokines tumour necrosis factor, interleukin-1 beta and interleukin-6 were also greatly enhanced in IL-10KO mice in comparison to wild-type mice. Liver histology from IL-10KO and IL-10WT did not show any parenchymal and portal tract inflammation at 4 days after DNBS administration. Serum total bilirubin and Alanine aminotransferase, were significantly increased in DNBS-IL-10KO mice vs. DNBS-IL-10KO mice. Therefore, we found an increase of tight junctional permeability to lanthanum nitrate (molecular weight, 433) in the livers from DNBS-treated IL-10WT mice; lanthanum accumulated throughout the junctional area up to the most apical region bordering the lumen. Absence of a functional IL-10 gene in IL-10KO mice resulted in a significant augmentation of apical diffusion of lanthanum after DNBS-induced colitis. Immunofluorescent labelling of frozen liver sections from DNBS-IL10KO mice, immunolocalization for and claudin-1 and ZO-1 resulted in a significant alteration in the localization of the immunosignals for claudin-1 and ZO-1 after DNBS administration in comparison with DNBS-IL10WT.
  
  
  CONCLUSIONS
  In conclusion, we suggest that the absence of IL-10 may represent an important pathophysiological mechanism of hepatobiliary injuries and cholestasis observed in patients with IBD.
authors.affiliation: Department of Biomorphology, School of Medicine, Messina, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Domenico
authors.initials: D
authors.lastname: Puzzolo
authors.forename: Achille P
authors.initials: AP
authors.lastname: Caputi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000818:Animals; D001557:Benzenesulfonates; D001663:Bilirubin / Q000097:blood; D003092:Colitis / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D003106:Colon / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D016753:Interleukin-10 / Q000502:physiology*; D007811:Lanthanum / Q000493:pharmacokinetics; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019108:Tight Junctions / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D001557:Benzenesulfonates; D016207:Cytokines; C007488:dinitrobenzenesulfonic acid; D016753:Interleukin-10; D007811:Lanthanum; D000410:Alanine Transaminase; D001663:Bilirubin