Opposing Regulation of the Tight Junction Protein Claudin-2 by Interferon-γ and Interleukin-4

Douglas M. Wisner, Leonard R. Harris, Cecelia L. Green, Lisa Poritz

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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 (IFNγ) and interleukin-4 (IL-4) negatively regulate each other and may have opposing roles in inflammatory bowel disease. Hypothesis: IFNγ and IL-4 will have opposing effects on the expression of claudin-2. Methods: Confluent T84 monolayers were apically incubated with IFNγ 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 IFNγ 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 IFNγ 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 IFNγ. Transepithelial resistance across T84 monolayers increased with IFNγ and decreased with IL-4. T84 monolayer permeability increased with IL-4 but not with IFNγ. 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 IFNγ 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.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalJournal of Surgical Research
Volume144
Issue number1
DOIs
StatePublished - Jan 1 2008

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Zonula Occludens-2 Protein
Claudin-2
Interleukin-4
Interferons
Interferon-gamma
Tight Junctions
Permeability
Inflammatory Bowel Diseases
Western Blotting
Claudins
Tight Junction Proteins
Fluorescent Antibody Technique
Analysis of Variance

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Wisner, Douglas M. ; Harris, Leonard R. ; Green, Cecelia L. ; Poritz, Lisa. / Opposing Regulation of the Tight Junction Protein Claudin-2 by Interferon-γ and Interleukin-4. In: Journal of Surgical Research. 2008 ; Vol. 144, No. 1. pp. 1-7.
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abstract = "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 (IFNγ) and interleukin-4 (IL-4) negatively regulate each other and may have opposing roles in inflammatory bowel disease. Hypothesis: IFNγ and IL-4 will have opposing effects on the expression of claudin-2. Methods: Confluent T84 monolayers were apically incubated with IFNγ 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 IFNγ 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 IFNγ 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 IFNγ. Transepithelial resistance across T84 monolayers increased with IFNγ and decreased with IL-4. T84 monolayer permeability increased with IL-4 but not with IFNγ. 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 IFNγ 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.",
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Opposing Regulation of the Tight Junction Protein Claudin-2 by Interferon-γ and Interleukin-4. / Wisner, Douglas M.; Harris, Leonard R.; Green, Cecelia L.; Poritz, Lisa.

In: Journal of Surgical Research, Vol. 144, No. 1, 01.01.2008, p. 1-7.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Opposing Regulation of the Tight Junction Protein Claudin-2 by Interferon-γ and Interleukin-4

AU - Wisner, Douglas M.

AU - Harris, Leonard R.

AU - Green, Cecelia L.

AU - Poritz, Lisa

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N2 - 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 (IFNγ) and interleukin-4 (IL-4) negatively regulate each other and may have opposing roles in inflammatory bowel disease. Hypothesis: IFNγ and IL-4 will have opposing effects on the expression of claudin-2. Methods: Confluent T84 monolayers were apically incubated with IFNγ 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 IFNγ 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 IFNγ 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 IFNγ. Transepithelial resistance across T84 monolayers increased with IFNγ and decreased with IL-4. T84 monolayer permeability increased with IL-4 but not with IFNγ. 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 IFNγ 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.

AB - 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 (IFNγ) and interleukin-4 (IL-4) negatively regulate each other and may have opposing roles in inflammatory bowel disease. Hypothesis: IFNγ and IL-4 will have opposing effects on the expression of claudin-2. Methods: Confluent T84 monolayers were apically incubated with IFNγ 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 IFNγ 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 IFNγ 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 IFNγ. Transepithelial resistance across T84 monolayers increased with IFNγ and decreased with IL-4. T84 monolayer permeability increased with IL-4 but not with IFNγ. 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 IFNγ 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.

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