Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells

Claudin proteins comprise a recently described family of tight junction proteins that differentially regulate paracellular permeability. Since other tight junction proteins show alterations in distribution or expression in inflammatory bowel disease (IBD) we assessed expression of claudins (CL) 2, 3...

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Bibliographic Details
Published in:Laboratory investigation 2005-09, Vol.85 (9), p.1139-1162
Main Authors: PRASAD, Shyam, MINGRINO, Roberto, KAUKINEN, Katri, HAYES, Katherine L, POWELL, Robert M, MACDONALD, Thomas T, COLLINS, Jane E
Format: Article
Language:English
Subjects:
Base Sequence
Biological and medical sciences
Biotechnology
Blotting, Western
Cell Division
Chromones - pharmacology
Claudin-3
Claudin-4
Claudins
Colon - cytology
Colon - physiopathology
DNA Primers
Electrophoresis, Polyacrylamide Gel
Enzyme Inhibitors - pharmacology
Epithelial Cells - physiology
Fundamental and applied biological sciences. Psychology
Humans
Immunohistochemistry
Inflammation Mediators - physiology
Interferon-gamma - physiology
Interleukin-13 - antagonists & inhibitors
Interleukin-13 - physiology
Intestinal Mucosa - physiopathology
Investigative techniques, diagnostic techniques (general aspects)
Medical sciences
Membrane Proteins - physiology
Morpholines - pharmacology
Phosphoinositide-3 Kinase Inhibitors
Reverse Transcriptase Polymerase Chain Reaction
Tumor Necrosis Factor-alpha - physiology
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Summary:Claudin proteins comprise a recently described family of tight junction proteins that differentially regulate paracellular permeability. Since other tight junction proteins show alterations in distribution or expression in inflammatory bowel disease (IBD) we assessed expression of claudins (CL) 2, 3 and 4 in IBD. CL 2 was strongly expressed along the inflamed crypt epithelium, whilst absent or barely detectable in normal colon. In contrast, CL 3 and 4 were present throughout normal colonic epithelium and were reduced or redistributed in the diseased surface epithelium. In a T84-cell culture model of the gut barrier, paracellular permeability decreased with time after plating and correlated with a marked decrease in the expression of CL 2. Addition of IFNgamma/TNFalpha led to further decreases in CL 2 and 3, the redistrbution of CL 4 and a marked increase in paracellular permeability. Conversely, IL-13 dramatically increased CL 2, with little effect on CL 3 or 4, but also resulted in increased paracellular permeability. Expression of CL 2 did not correlate with proliferation or junctional reorganisation after calcium ion depletion. Re-expression of CL 2 in response to IL-13 was inhibited by phophatidylinositol 3 kinase inhibitor, LY294002, which also restored the ion permeability to previous levels. CL 2 expression could be stimulated in the absence of IL-13 by activation of phospho-Akt in the phophatidylinositol 3 kinase pathway. These results suggest that INFgamma/TNFalpha and IL-13 have differential effects on CL 2, 3 and 4 in tight junctions, which may lead to increased permeability via different mechanisms.
ISSN:0023-6837
1530-0307
DOI:10.1038/labinvest.3700316