| Paracellular permeability is increased by basal lipopolysaccharide in a primary culture of colonic epithelial cells; an effect prevented by an activator of Toll-like receptor-2. | |
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MedLine Citation:
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PMID: 20472611 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Lipopolysaccharide (LPS), which generally activates Toll-like receptor 4 (TLR4), is expressed on commensal colonic bacteria. In a number of tissues, LPS can act directly on epithelial cells to increase paracellular permeability. Such an effect in the colon would have an important impact on the understanding of normal homeostasis and of pathology. Our aim was to use a novel primary culture of colonic epithelial cells grown on Transwells to investigate whether LPS, or Pam(3)CSK( 4), an activator of TLR2, affected paracellular permeability. Consequently, [(14)C]-mannitol transfer and transepithelial electrical resistance (TEER) were measured. The preparation consisted primarily of cytokeratin-18 positive epithelial cells that produced superoxide, stained for mucus with periodic acid-Schiff reagent, exhibited alkaline phosphatase activity and expressed TLR2 and TLR4. Tight junctions and desmosomes were visible by transmission electron microscopy. Basally, but not apically, applied LPS from Escherichia coli increased the permeability to mannitol and to a 10-kDa dextran, and reduced TEER. The LPS from Helicobacter pylori increased paracellular permeability of gastric cells when applied either apically or basally, in contrast to colon cells, where this LPS was active only from the basal aspect. A pan-caspase inhibitor prevented the increase in caspase activity caused by basal E. coli LPS, and reduced the effects of LPS on paracellular permeability. Synthetic Pam(3)CSK(4) in the basal compartment prevented all effects of basal E. coli LPS. In conclusion, LPS applied to the base of the colonic epithelial cells increased paracellular permeability by a mechanism involving caspase activation, suggesting a process by which perturbation of the gut barrier could be exacerbated. Moreover, activation of TLR2 ameliorated such effects. |
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Authors:
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Peter J Hanson; Anthony P Moran; Kate Butler |
Publication Detail:
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Type: Journal Article Date: 2010-05-14 |
Journal Detail:
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Title: Innate immunity Volume: 17 ISSN: 1753-4267 ISO Abbreviation: Innate Immun Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-06-06 Completed Date: 2011-10-21 Revised Date: 2012-02-22 |
Medline Journal Info:
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Nlm Unique ID: 101469670 Medline TA: Innate Immun Country: United States |
Other Details:
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Languages: eng Pagination: 269-82 Citation Subset: IM |
Affiliation:
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Life and Health Sciences, Aston University, Birmingham, UK. p.j.hanson@aston.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Caco-2 Cells Cell Culture Techniques Cell Membrane Permeability / drug effects Cell Polarity Colon / pathology Enterocytes / drug effects, physiology* Epithelial Cells / drug effects, physiology* Escherichia coli / metabolism* Guinea Pigs Helicobacter pylori / metabolism* Humans Lipopeptides / pharmacology Lipopolysaccharides / pharmacology Mannitol / pharmacology Species Specificity Toll-Like Receptor 2 / agonists, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Lipopeptides; 0/Lipopolysaccharides; 0/Pam(3)CSK(4) peptide; 0/Toll-Like Receptor 2; 69-65-8/Mannitol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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