Document Detail

Opposing regulation of the tight junction protein claudin-2 by interferon-gamma and interleukin-4.
MedLine Citation:
PMID:  17640674     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The claudins are tight junction (TJ) proteins. Claudin-2 has been found to negatively affect the TJ, causing a decrease in transepithelial resistance. Patients with inflammatory bowel disease have altered intestinal permeability, suggesting a TJ disruption. Interferon-gamma (IFNgamma) and interleukin-4 (IL-4) negatively regulate each other and may have opposing roles in inflammatory bowel disease.
HYPOTHESIS: IFNgamma and IL-4 will have opposing effects on the expression of claudin-2.
METHODS: Confluent T84 monolayers were apically incubated with IFNgamma or IL-4. The monolayers were immunofluorescently stained or lysed for Western blot with anti-claudin-2 or -4. Additional monolayers were grown on transwell plates, treated with IFNgamma or IL-4, measured for changes in transepithelial resistance, and assayed for changes in permeability using FITC-dextran-4000. Statistics were calculated by analysis of variance.
RESULTS: Addition of IFNgamma to T84 monolayers resulted in decreased claudin-2 and addition of IL-4 resulted in increased claudin-2 by Western blot. By immunofluorescence, there was a loss of claudin-2 from the membrane in cells treated with IFNgamma. Transepithelial resistance across T84 monolayers increased with IFNgamma and decreased with IL-4. T84 monolayer permeability increased with IL-4 but not with IFNgamma.
CONCLUSIONS: Incubation of T84 cells with IL-4 leads to increased claudin-2 with a corresponding decrease in transepithelial resistance and increase in permeability. Incubation of T84 cells with IFNgamma leads to decreased claudin-2 and increased transepithelial resistance. These cytokines have opposite effects on the expression of claudin-2 and the physiology of the TJ.
Douglas M Wisner; Leonard R Harris; Cecelia L Green; Lisa S Poritz
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Publication Detail:
Type:  Journal Article     Date:  2007-07-19
Journal Detail:
Title:  The Journal of surgical research     Volume:  144     ISSN:  0022-4804     ISO Abbreviation:  J. Surg. Res.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2007-12-17     Completed Date:  2008-02-15     Revised Date:  2014-07-30    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1-7     Citation Subset:  IM    
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MeSH Terms
Blotting, Western
Cell Line
Electric Impedance
Fluorescent Antibody Technique
Inflammatory Bowel Diseases / metabolism*
Interferon-gamma / metabolism*,  pharmacology
Interleukin-4 / metabolism*,  pharmacology
Intestinal Mucosa / cytology,  immunology,  metabolism
Membrane Proteins / metabolism*
Permeability / drug effects
Tight Junctions / drug effects,  immunology,  metabolism*
Reg. No./Substance:
0/CLDN2 protein, human; 0/Claudins; 0/IL4 protein, human; 0/Membrane Proteins; 207137-56-2/Interleukin-4; 82115-62-6/Interferon-gamma

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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