Document Detail


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.
MedLine Citation:
PMID:  20472611     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Peter J Hanson; Anthony P Moran; Kate Butler
Publication Detail:
Type:  Journal Article     Date:  2010-05-14
Journal Detail:
Title:  Innate immunity     Volume:  17     ISSN:  1753-4267     ISO Abbreviation:  Innate Immun     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-06-06     Completed Date:  2011-10-21     Revised Date:  2012-02-22    
Medline Journal Info:
Nlm Unique ID:  101469670     Medline TA:  Innate Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  269-82     Citation Subset:  IM    
Affiliation:
Life and Health Sciences, Aston University, Birmingham, UK. p.j.hanson@aston.ac.uk
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MeSH Terms
Descriptor/Qualifier:
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:
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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