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Increased T-helper 2 cytokines in bile from patients with IgG4-related cholangitis disrupt the tight junction-associated biliary epithelial cell barrier

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Increased T-helper 2 cytokines in bile from patients with IgG4-related cholangitis disrupt the tight junction-associated biliary epithelial cell barrier. / Müller, Tobias; Beutler, Claudia; Picó, Almudena Hurtado; Otten, Morgane; Dürr, Angelika; Al-Abadi, Hussain; Guckelberger, Olaf; Meyer Zum Büschenfelde, Dirk; Jöhrens, Korinna; Volkmann, Martin; Lankisch, Tim; Voigtländer, Torsten; Anders, Mario; Shibolet, Oren; Jefferson, Douglas M; Podolsky, Daniel K; Fischer, Andreas; Veltzke-Schlieker, Wilfried; Adler, Andreas; Baumgart, Daniel C; Sturm, Andreas; Wiedenmann, Bertram; Schott, Eckart; Berg, Thomas.

In: GASTROENTEROLOGY, Vol. 144, No. 5, 01.05.2013, p. 1116-28.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Müller, T, Beutler, C, Picó, AH, Otten, M, Dürr, A, Al-Abadi, H, Guckelberger, O, Meyer Zum Büschenfelde, D, Jöhrens, K, Volkmann, M, Lankisch, T, Voigtländer, T, Anders, M, Shibolet, O, Jefferson, DM, Podolsky, DK, Fischer, A, Veltzke-Schlieker, W, Adler, A, Baumgart, DC, Sturm, A, Wiedenmann, B, Schott, E & Berg, T 2013, 'Increased T-helper 2 cytokines in bile from patients with IgG4-related cholangitis disrupt the tight junction-associated biliary epithelial cell barrier', GASTROENTEROLOGY, vol. 144, no. 5, pp. 1116-28. https://doi.org/10.1053/j.gastro.2013.01.055

APA

Müller, T., Beutler, C., Picó, A. H., Otten, M., Dürr, A., Al-Abadi, H., Guckelberger, O., Meyer Zum Büschenfelde, D., Jöhrens, K., Volkmann, M., Lankisch, T., Voigtländer, T., Anders, M., Shibolet, O., Jefferson, D. M., Podolsky, D. K., Fischer, A., Veltzke-Schlieker, W., Adler, A., ... Berg, T. (2013). Increased T-helper 2 cytokines in bile from patients with IgG4-related cholangitis disrupt the tight junction-associated biliary epithelial cell barrier. GASTROENTEROLOGY, 144(5), 1116-28. https://doi.org/10.1053/j.gastro.2013.01.055

Vancouver

Müller T, Beutler C, Picó AH, Otten M, Dürr A, Al-Abadi H et al. Increased T-helper 2 cytokines in bile from patients with IgG4-related cholangitis disrupt the tight junction-associated biliary epithelial cell barrier. GASTROENTEROLOGY. 2013 May 1;144(5):1116-28. https://doi.org/10.1053/j.gastro.2013.01.055

Bibtex

@article{43ed31b3a43f4254bc6318c52938104a,
title = "Increased T-helper 2 cytokines in bile from patients with IgG4-related cholangitis disrupt the tight junction-associated biliary epithelial cell barrier",
abstract = "BACKGROUND & AIMS: IgG4-related cholangitis is a chronic inflammatory biliary disease that involves different parts of the pancreatobiliary system, but little is known about its mechanisms of pathogenesis. A T-helper (Th) 2 cell cytokine profile predominates in liver tissues from these patients. We investigated whether Th2 cytokines disrupt the barrier function of biliary epithelial cells (BECs) in patients with IgG4-related cholangitis.METHODS: We assessed the Th2 cytokine profile in bile samples and brush cytology samples from 16 patients with IgG4-related cholangitis and respective controls, and evaluated transcription of tight junction (TJ)-associated proteins in primary BECs from these patients. The effect of Th2 cytokines on TJ-mediated BEC barrier function and wound closure was examined by immunoblot, transepithelial resistance, charge-selective Na(+)/Cl(-) permeability, and 4-kDa dextran flux analyses.RESULTS: Bile samples from patients with IgG4-related cholangitis had significant increases in levels of Th2 cytokines, interleukin (IL)-4, and IL-5. IL-13 was not detected in bile samples, but polymerase chain reaction analysis of whole-brush cytology samples from patients with IgG4-related cholangitis revealed increased levels of IL-13 mRNA, compared with controls. BECs isolated from the brush cytology samples revealed decreased levels of claudin-1 and increased levels of claudin-2 mRNAs. In vitro, IL-4 and IL-13 significantly reduced TJ-associated BEC barrier function by activating claudin-2-mediated paracellular pore pathways. Th2 cytokines also impaired wound closure in BEC monolayers.CONCLUSIONS: Th2 cytokines predominate in bile samples from patients with IgG4-related cholangitis and disrupt the TJ-mediated BEC barrier in vitro. Subsequent increases in biliary leaks might contribute to the pathogenesis of chronic biliary inflammation in these patients.",
keywords = "Adult, Aged, Aged, 80 and over, Antibodies, Anti-Idiotypic, Bile, Blotting, Western, Cell Membrane Permeability, Cells, Cultured, Cholangitis, Cytokines, Enzyme-Linked Immunosorbent Assay, Epithelial Cells, Female, Humans, Immunity, Cellular, Immunoglobulin G, Male, Middle Aged, Th2 Cells, Tight Junctions",
author = "Tobias M{\"u}ller and Claudia Beutler and Pic{\'o}, {Almudena Hurtado} and Morgane Otten and Angelika D{\"u}rr and Hussain Al-Abadi and Olaf Guckelberger and {Meyer Zum B{\"u}schenfelde}, Dirk and Korinna J{\"o}hrens and Martin Volkmann and Tim Lankisch and Torsten Voigtl{\"a}nder and Mario Anders and Oren Shibolet and Jefferson, {Douglas M} and Podolsky, {Daniel K} and Andreas Fischer and Wilfried Veltzke-Schlieker and Andreas Adler and Baumgart, {Daniel C} and Andreas Sturm and Bertram Wiedenmann and Eckart Schott and Thomas Berg",
note = "Copyright {\textcopyright} 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.",
year = "2013",
month = may,
day = "1",
doi = "10.1053/j.gastro.2013.01.055",
language = "English",
volume = "144",
pages = "1116--28",
journal = "GASTROENTEROLOGY",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "5",

}

RIS

TY - JOUR

T1 - Increased T-helper 2 cytokines in bile from patients with IgG4-related cholangitis disrupt the tight junction-associated biliary epithelial cell barrier

AU - Müller, Tobias

AU - Beutler, Claudia

AU - Picó, Almudena Hurtado

AU - Otten, Morgane

AU - Dürr, Angelika

AU - Al-Abadi, Hussain

AU - Guckelberger, Olaf

AU - Meyer Zum Büschenfelde, Dirk

AU - Jöhrens, Korinna

AU - Volkmann, Martin

AU - Lankisch, Tim

AU - Voigtländer, Torsten

AU - Anders, Mario

AU - Shibolet, Oren

AU - Jefferson, Douglas M

AU - Podolsky, Daniel K

AU - Fischer, Andreas

AU - Veltzke-Schlieker, Wilfried

AU - Adler, Andreas

AU - Baumgart, Daniel C

AU - Sturm, Andreas

AU - Wiedenmann, Bertram

AU - Schott, Eckart

AU - Berg, Thomas

N1 - Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

PY - 2013/5/1

Y1 - 2013/5/1

N2 - BACKGROUND & AIMS: IgG4-related cholangitis is a chronic inflammatory biliary disease that involves different parts of the pancreatobiliary system, but little is known about its mechanisms of pathogenesis. A T-helper (Th) 2 cell cytokine profile predominates in liver tissues from these patients. We investigated whether Th2 cytokines disrupt the barrier function of biliary epithelial cells (BECs) in patients with IgG4-related cholangitis.METHODS: We assessed the Th2 cytokine profile in bile samples and brush cytology samples from 16 patients with IgG4-related cholangitis and respective controls, and evaluated transcription of tight junction (TJ)-associated proteins in primary BECs from these patients. The effect of Th2 cytokines on TJ-mediated BEC barrier function and wound closure was examined by immunoblot, transepithelial resistance, charge-selective Na(+)/Cl(-) permeability, and 4-kDa dextran flux analyses.RESULTS: Bile samples from patients with IgG4-related cholangitis had significant increases in levels of Th2 cytokines, interleukin (IL)-4, and IL-5. IL-13 was not detected in bile samples, but polymerase chain reaction analysis of whole-brush cytology samples from patients with IgG4-related cholangitis revealed increased levels of IL-13 mRNA, compared with controls. BECs isolated from the brush cytology samples revealed decreased levels of claudin-1 and increased levels of claudin-2 mRNAs. In vitro, IL-4 and IL-13 significantly reduced TJ-associated BEC barrier function by activating claudin-2-mediated paracellular pore pathways. Th2 cytokines also impaired wound closure in BEC monolayers.CONCLUSIONS: Th2 cytokines predominate in bile samples from patients with IgG4-related cholangitis and disrupt the TJ-mediated BEC barrier in vitro. Subsequent increases in biliary leaks might contribute to the pathogenesis of chronic biliary inflammation in these patients.

AB - BACKGROUND & AIMS: IgG4-related cholangitis is a chronic inflammatory biliary disease that involves different parts of the pancreatobiliary system, but little is known about its mechanisms of pathogenesis. A T-helper (Th) 2 cell cytokine profile predominates in liver tissues from these patients. We investigated whether Th2 cytokines disrupt the barrier function of biliary epithelial cells (BECs) in patients with IgG4-related cholangitis.METHODS: We assessed the Th2 cytokine profile in bile samples and brush cytology samples from 16 patients with IgG4-related cholangitis and respective controls, and evaluated transcription of tight junction (TJ)-associated proteins in primary BECs from these patients. The effect of Th2 cytokines on TJ-mediated BEC barrier function and wound closure was examined by immunoblot, transepithelial resistance, charge-selective Na(+)/Cl(-) permeability, and 4-kDa dextran flux analyses.RESULTS: Bile samples from patients with IgG4-related cholangitis had significant increases in levels of Th2 cytokines, interleukin (IL)-4, and IL-5. IL-13 was not detected in bile samples, but polymerase chain reaction analysis of whole-brush cytology samples from patients with IgG4-related cholangitis revealed increased levels of IL-13 mRNA, compared with controls. BECs isolated from the brush cytology samples revealed decreased levels of claudin-1 and increased levels of claudin-2 mRNAs. In vitro, IL-4 and IL-13 significantly reduced TJ-associated BEC barrier function by activating claudin-2-mediated paracellular pore pathways. Th2 cytokines also impaired wound closure in BEC monolayers.CONCLUSIONS: Th2 cytokines predominate in bile samples from patients with IgG4-related cholangitis and disrupt the TJ-mediated BEC barrier in vitro. Subsequent increases in biliary leaks might contribute to the pathogenesis of chronic biliary inflammation in these patients.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibodies, Anti-Idiotypic

KW - Bile

KW - Blotting, Western

KW - Cell Membrane Permeability

KW - Cells, Cultured

KW - Cholangitis

KW - Cytokines

KW - Enzyme-Linked Immunosorbent Assay

KW - Epithelial Cells

KW - Female

KW - Humans

KW - Immunity, Cellular

KW - Immunoglobulin G

KW - Male

KW - Middle Aged

KW - Th2 Cells

KW - Tight Junctions

U2 - 10.1053/j.gastro.2013.01.055

DO - 10.1053/j.gastro.2013.01.055

M3 - SCORING: Journal article

C2 - 23391819

VL - 144

SP - 1116

EP - 1128

JO - GASTROENTEROLOGY

JF - GASTROENTEROLOGY

SN - 0016-5085

IS - 5

ER -