Microbial Products Induce Claudin-2 to Compromise Gut Epithelial Barrier Function

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Aug 31

PMID 23990874

Citations 27

Authors

Xiaoyu Liu

Gui Yang

Xiao-Rui Geng

Yanjuan Cao

Na Li

Li Ma

Si Chen

Ping-Chang Yang

Zhigang Liu

Affiliations

Soon will be listed here.

Abstract

The epithelial barrier dysfunction is an important pathogenic feature in a number of diseases. The underlying mechanism is to be further investigated. The present study aims to investigate the role of tight junction protein claudin-2 (Cldn2) in the compromising epithelial barrier function. In this study, the expression of Cldn2 in the epithelial layer of mice and patients with food allergy was observed by immunohistochemistry. The induction of Cldn2 was carried out with a cell culture model. The Cldn2-facilitated antigen internalization was observed by confocal microscopy. The epithelial barrier function in the gut epithelial monolayer was assessed by recording the transepithelial resistance and assessing the permeability to a macromolecular tracer. The results showed that the positive immune staining of Cldn2 was observed in the epithelial layer of the small intestine that was weakly stained in naïve control mice, and strongly stained in sensitized mice as well as patients with food allergy. Exposure to cholera toxin or Staphylococcal enterotoxin B induced the expression of Cldn2 in HT-29 or T84 cells. Cldn2 could bind protein antigen to form complexes to facilitate the antigen transport across the epithelial barrier. Blocking Cldn2 prevented the allergen-related hypersensitivity the intestine. We conclude that the tight junction protein Cldn2 is involved in the epithelial barrier dysfunction.

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References

Goto Y, Kiyono H . Epithelial barrier: an interface for the cross-communication between gut flora and immune system. Immunol Rev. 2011; 245(1):147-63. DOI: 10.1111/j.1600-065X.2011.01078.x. View

Wang W, Tsai J, Kuo C, Chen H, Kao S . Non-proteolytic house dust mite allergen, Der p 2, upregulated expression of tight junction molecule claudin-2 associated with Akt/GSK-3β/β-catenin signaling pathway. J Cell Biochem. 2011; 112(6):1544-51. DOI: 10.1002/jcb.23067. View

Yang P, Xing Z, Berin C, Soderholm J, Feng B, Wu L . TIM-4 expressed by mucosal dendritic cells plays a critical role in food antigen-specific Th2 differentiation and intestinal allergy. Gastroenterology. 2007; 133(5):1522-33. DOI: 10.1053/j.gastro.2007.08.006. View

McKay D, Singh P . Superantigen activation of immune cells evokes epithelial (T84) transport and barrier abnormalities via IFN-gamma and TNF alpha: inhibition of increased permeability, but not diminished secretory responses by TGF-beta2. J Immunol. 1997; 159(5):2382-90. View

Yu L, Yang P, Berin M, Di Leo V, Conrad D, McKay D . Enhanced transepithelial antigen transport in intestine of allergic mice is mediated by IgE/CD23 and regulated by interleukin-4. Gastroenterology. 2001; 121(2):370-81. DOI: 10.1053/gast.2001.26470. View

Bailon E, Cueto-Sola M, Utrilla P, Rodriguez-Ruiz J, Garrido-Mesa N, Zarzuelo A . A shorter and more specific oral sensitization-based experimental model of food allergy in mice. J Immunol Methods. 2012; 381(1-2):41-9. DOI: 10.1016/j.jim.2012.04.007. View

Bu H, Wang X, Tang Y, Koti V, Tan X . Toll-like receptor 2-mediated peptidoglycan uptake by immature intestinal epithelial cells from apical side and exosome-associated transcellular transcytosis. J Cell Physiol. 2009; 222(3):658-68. PMC: 4414048. DOI: 10.1002/jcp.21985. View

Meertens L, Bertaux C, Cukierman L, Cormier E, Lavillette D, Cosset F . The tight junction proteins claudin-1, -6, and -9 are entry cofactors for hepatitis C virus. J Virol. 2008; 82(7):3555-60. PMC: 2268462. DOI: 10.1128/JVI.01977-07. View

Feng B, Chen X, He S, Zheng P, Foster J, Xing Z . Disruption of T-cell immunoglobulin and mucin domain molecule (TIM)-1/TIM4 interaction as a therapeutic strategy in a dendritic cell-induced peanut allergy model. J Allergy Clin Immunol. 2008; 122(1):55-61, 61.e1-7. DOI: 10.1016/j.jaci.2008.04.036. View

10.

Knauf F, Ko N, Jiang Z, Robertson W, Van Itallie C, Anderson J . Net intestinal transport of oxalate reflects passive absorption and SLC26A6-mediated secretion. J Am Soc Nephrol. 2011; 22(12):2247-55. PMC: 3250206. DOI: 10.1681/ASN.2011040433. View

11.

Vetrano S, Ploplis V, Sala E, Sandoval-Cooper M, Donahue D, Correale C . Unexpected role of anticoagulant protein C in controlling epithelial barrier integrity and intestinal inflammation. Proc Natl Acad Sci U S A. 2011; 108(49):19830-5. PMC: 3241765. DOI: 10.1073/pnas.1107140108. View

12.

Larre I, Castillo A, Flores-Maldonado C, Contreras R, Galvan I, Munoz-Estrada J . Ouabain modulates ciliogenesis in epithelial cells. Proc Natl Acad Sci U S A. 2011; 108(51):20591-6. PMC: 3251114. DOI: 10.1073/pnas.1102617108. View

13.

Kearney D, Wang W, Redmond H, Wang J . Bacterial superantigens enhance the in vitro proinflammatory response and in vivo lethality of the TLR2 agonist bacterial lipoprotein. J Immunol. 2011; 187(10):5363-9. DOI: 10.4049/jimmunol.1003747. View

14.

Denizot J, Sivignon A, Barreau F, Darcha C, Chan H, Stanners C . Adherent-invasive Escherichia coli induce claudin-2 expression and barrier defect in CEABAC10 mice and Crohn's disease patients. Inflamm Bowel Dis. 2011; 18(2):294-304. DOI: 10.1002/ibd.21787. View

15.

Lee A, Gibson D, Zhang Y, Sham H, Vallance B, Dutz J . Gut barrier disruption by an enteric bacterial pathogen accelerates insulitis in NOD mice. Diabetologia. 2009; 53(4):741-8. DOI: 10.1007/s00125-009-1626-y. View

16.

Furuse M . Molecular basis of the core structure of tight junctions. Cold Spring Harb Perspect Biol. 2010; 2(1):a002907. PMC: 2827901. DOI: 10.1101/cshperspect.a002907. View

17.

Gunther C, Martini E, Wittkopf N, Amann K, Weigmann B, Neumann H . Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis. Nature. 2011; 477(7364):335-9. PMC: 3373730. DOI: 10.1038/nature10400. View

18.

Yang P, Jury J, Soderholm J, Sherman P, McKay D, Perdue M . Chronic psychological stress in rats induces intestinal sensitization to luminal antigens. Am J Pathol. 2006; 168(1):104-14. PMC: 1592661. DOI: 10.2353/ajpath.2006.050575. View

19.

Mallegol J, van Niel G, Lebreton C, Lepelletier Y, Candalh C, Dugave C . T84-intestinal epithelial exosomes bear MHC class II/peptide complexes potentiating antigen presentation by dendritic cells. Gastroenterology. 2007; 132(5):1866-76. DOI: 10.1053/j.gastro.2007.02.043. View

20.

Snoek S, Verstege M, Boeckxstaens G, van den Wijngaard R, de Jonge W . The enteric nervous system as a regulator of intestinal epithelial barrier function in health and disease. Expert Rev Gastroenterol Hepatol. 2010; 4(5):637-51. DOI: 10.1586/egh.10.51. View