| Role of IL-10 in hepatocyte tight junction alteration in mouse model of experimental colitis. | |
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MedLine Citation:
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PMID: 12393933 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. MATERIALS AND 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. CONCLUSION: 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. |
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Authors:
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Emanuela Mazzon; Domenico Puzzolo; Achille P Caputi; Salvatore Cuzzocrea |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Molecular medicine (Cambridge, Mass.) Volume: 8 ISSN: 1076-1551 ISO Abbreviation: Mol. Med. Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-10-23 Completed Date: 2003-04-16 Revised Date: 2008-11-20 |
Medline Journal Info:
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Nlm Unique ID: 9501023 Medline TA: Mol Med Country: United States |
Other Details:
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Languages: eng Pagination: 353-66 Citation Subset: IM |
Affiliation:
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Department of Biomorphology, School of Medicine, Messina, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alanine Transaminase
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blood,
drug effects Animals Benzenesulfonates Bilirubin / blood Colitis / chemically induced, pathology*, physiopathology Colon / drug effects, pathology, physiopathology Cytokines / analysis Disease Models, Animal* Hepatocytes / drug effects, pathology*, ultrastructure Interleukin-10 / physiology* Lanthanum / pharmacokinetics Liver / drug effects, pathology, physiopathology Mice Mice, Inbred C57BL Mice, Knockout Tight Junctions / drug effects, pathology*, ultrastructure |
| Chemical | |
Reg. No./Substance:
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0/Benzenesulfonates; 0/Cytokines; 12379-41-8/dinitrobenzenesulfonic acid; 130068-27-8/Interleukin-10; 635-65-4/Bilirubin; 7439-91-0/Lanthanum; EC 2.6.1.2/Alanine Transaminase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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