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

Record type: Article

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 IFN/TNF 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 INF/TNF and IL-13 have differential effects on CL 2, 3 and 4 in tight junctions, which may lead to increased permeability via different mechanisms.

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Citation

Prasad, Shyam, Mingrino, Roberto, Kaukinen, Katri, Hayes, Katherine L., Powell, Robert M., MacDonald, Thomas T and Collins, Jane E. (2005) Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells Laboratory Investigation, 85, (9), pp. 1139-1162. (doi:10.1038/labinvest.3700316). (PMID:16007110).

More information

Published date: 11 July 2005
Keywords: claudin, tight junction, tnf/inf, il-13
Organisations: Infection Inflammation & Immunity

Identifiers

Local EPrints ID: 180177
URI: http://eprints.soton.ac.uk/id/eprint/180177
ISSN: 0023-6837
PURE UUID: 69c781ea-dc25-4e27-81d4-fe2d0f1c508c

Catalogue record

Date deposited: 05 Apr 2011 13:57
Last modified: 18 Jul 2017 12:01

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Contributors

Author: Shyam Prasad
Author: Roberto Mingrino
Author: Katri Kaukinen
Author: Katherine L. Hayes
Author: Robert M. Powell
Author: Thomas T MacDonald
Author: Jane E. Collins

University divisions


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