Intestinal barrier function: Molecular regulation and disease pathogenesis

Journal of Allergy and Clinical Immunology

Volumn 124, Issue 1, 2009, Pages 3-20

  Groschwitz, Katherine R ^a,b   Hogan, Simon P ^a  

^a UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

^b CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

Author keywords

Intestinal epithelium

Indexed keywords

ALCOHOL; CLAUDIN; CYTOKINE; JUNCTIONAL ADHESION MOLECULE A; NONSTEROID ANTIINFLAMMATORY AGENT; OCCLUDIN;

ADAPTIVE IMMUNITY; CELIAC DISEASE; CELL ADHESION; CELL JUNCTION; CLOSTRIDIUM PERFRINGENS; CROHN DISEASE; DIGESTIVE SYSTEM INJURY; DISEASE EXACERBATION; DISEASE PREDISPOSITION; ENTERITIS; ENTEROPATHOGENIC ESCHERICHIA COLI; EOSINOPHIL; FOOD ALLERGY; GASTROINTESTINAL TRACT; HUMAN; IMMUNOCOMPETENT CELL; INFLAMMATION; INNATE IMMUNITY; INSULIN DEPENDENT DIABETES MELLITUS; INTESTINE EPITHELIUM; INTESTINE MUCOSA PERMEABILITY; MAST CELL; MOLECULAR BIOLOGY; MOLECULAR INTERACTION; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN INTERACTION; REGULATORY MECHANISM; REVIEW; STRESS; STRUCTURE ANALYSIS; T LYMPHOCYTE; TIGHT JUNCTION; ULCERATIVE COLITIS; VIBRIO CHOLERAE;

HUMANS; INFLAMMATORY BOWEL DISEASES; INTERCELLULAR JUNCTIONS; INTESTINAL MUCOSA;

EID: 67649216750     PISSN: 00916749     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jaci.2009.05.038     Document Type: Review

References (260)

1. Blikslager A.T., Moeser A.J., Gookin J.L., Jones S.L., and Podle J. Restoration of barrier function in injured intestinal mucosa. Physiol Rev 87 (2007) 545-564
2. Podolsky D.K. Mucosal immunity and inflammation. V. Innate mechanisms of mucosal defense and repair: the best offense is a good defense. Am J Physiol Gastrointest Liver Physiol 277 (1999) G495-G499
3. Kunzelmann K., and Mall M. Electrolyte transport in the mammalian colon: mechanisms and implications for disease. Physiol Rev 82 (2002) 245-289
4. Broer S. Amino acid transport across mammalian intestinal and renal epithelia. Physiol Rev 88 (2008) 249-286
5. Ferraris R.P., and Diamond J. Regulation of intestinal sugar transport. Physiol Rev 77 (1997) 257-302
6. Tsukita S., Furuse M., and Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2 (2001) 285-293
7. Van Itallie C.M., and Anderson J.M. Claudins and epithelial paracellular transport. Annu Rev Physiol 68 (2006) 403-429
8. Farquher M.G., and Palade G.E. Junctional complexes in various epithelia. J Cell Biol 17 (1963) 375-412
9. Schneeberger E.E., and Lynch R.D. Structure, function, and regulation of cellular tight junctions. Am J Physiol Lung Cell Mol Physiol 262 (1992) L647-L661
10. Gumbiner B. Breaking through the tight junction barrier. J Cell Biol 123 (1993) 1631-1633
11. Hartsock A., and Nelson W.J. Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim Biophys Acta 1778 (2008) 660-669
12. Forster C. Tight junctions and the modulation of barrier function in disease. Histochem Cell Biol 130 (2008) 55-70
13. Harhaj N.S., and Antonetti D.A. Regulation of tight junction and loss of barrier function in pathophysiology. Int J Biochem Cell Biol 36 (2004) 1206-1237
14. Tsukita S., and Furuse M. The structure and function of claudins, cell adhesion molecules at tight junctions. Ann N Y Acad Sci 915 (2000) 129-135
15. Cereijido M., Contreras R.G., and Shoshani L. Cell adhesion, polarity and epithelia in the dawn of metazoans. Physiol Rev 84 (2004) 1229-1262
16. Weis W.I., and Nelson W.J. Re-solving the cadherin-catenin-actin conundrum. J Biol Chem 281 (2006) 35593-35597
17. Halbleib J.M., and Nelson W.J. Cadherins in development: cell adhesion, sorting, and tissue morphogenesis. Genes Dev 20 (2006) 3199-3214
18. Perez-Moreno M., and Fuchs E. Catenins: keeping cells from getting their signals crossed. Dev Cell 11 (2006) 601-612
19. Perez-Moreno M., Jamora C., and Fuchs E. Sticky business: orchestrating cellular signals at adherens junctions. Cell 112 (2003) 535-548
20. Gumbiner B.M. Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol 6 (2005) 622-634
21. Ebnet K. Organization of multiprotein complexes at cell-cell junctions. Histochem Cell Biol 130 (2008) 1-20
22. Vasioukhin V., Bauer C., Yin M., and Fuchs E. Directed actin polymerization is the driving force for epithelial cell-cell adhesion. Cell 100 (2000) 209-219
23. Vasioukhin V., Bowers E., Bauer C., Degenstein L., and Fuchs E. Desmoplakin is essential in epidermal sheet formation. Nat Cell Biol 3 (2001) 1076-1085
24. Ikeda W., Nakanishi H., Miyoshi J., Mandai K., Ishizaki H., Tanaka M., et al. Afadin: a key molecule essential for structural organization of cell-cell junctions of polarized epithelia during embryogenesis. J Cell Biol 146 (1999) 1117-1132
25. Pokutta S., and Weis W.I. The cytoplasmic face of cell contact sites. Curr Opin Struct Biol 12 (2002) 255-262
26. Pokutta S., and Weis W.I. Structure and mechanism of cadherins and catenins in cell-cell contacts. Annu Rev Cell Dev Biol 23 (2007) 237-261
27. Reynolds A.B., and Roczniak-Ferguson A. Emerging roles for p120-catenin in cell adhesion and cancer. Oncogene 23 (2004) 7947-7956
28. Hermiston M.L., and Gordon J.I. In vivo analysis of cadherin function in the mouse intestinal epithelium: essential roles in adhesion, maintenance of differentiation, and regulation of programmed cell death. J Cell Biol 129 (1995) 489-506
29. Herminston M.L., and Gordon J.I. Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Science 270 (1995) 1203-1207
30. Miyoshi J., and Takai Y. Nectin and nectin-like molecules: biology and pathology. Am J Nephrol 27 (2007) 590-604
31. Takai Y., Ikeda W., Ogita H., and Rikitake Y. The immunoglobulin-like cell adhesion molecule nectin and its associated protein afadin. Annu Rev Cell Dev Biol 24 (2008) 309-342
32. Sakisaka T., Ikeda W., Ogita H., Fujita N., and Takai Y. The roles of nectins in cell adhesions: cooperation with other cell adhesion molecules and growth factor receptors. Curr Opin Cell Biol 19 (2007) 593-602
33. Pokutta S., Drees F., Takai Y., Nelson W.J., and Weis W.I. Biochemical and structural definition of the l-afadin- and actin-binding sites of alpha-catenin. J Biol Chem 277 (2002) 18868-18874
34. Tachibana K., Nakanishi H., Mandai K., Ozaki K., Ikeda W., Yamamoto Y., et al. Two cell adhesion molecules, nectin and cadherin, interact through their cytoplasmic domain-associated proteins. J Cell Biol 150 (2000) 1161-1176
35. Mandai K., Nakanishi H., Satoh A., Takahashi K., Satoh K., Nishioka H., et al. Ponsin/SH3P12: an l-afadin- and vinculin-binding protein localized at cell-cell and cell-matrix adherens junctions. J Cell Biol 144 (1999) 1001-1017
36. Asada M., Irie K., Morimoto K., Yamada A., Ikeda W., Takeuchi M., et al. ADIP, a novel Afadin- and alpha-actinin-binding protein localized at cell-cell adherens junctions. J Biol Chem 278 (2003) 4103-4111
37. Ooshio T., Irie K., Morimoto K., Fukuhara A., Imai T., and Takai Y. Involvement of LMO7 in the association of two cell-cell adhesion molecules, nectin and E-cadherin, through afadin and alpha-actinin in epithelial cells. J Biol Chem 279 (2004) 31365-31373
38. Gonzalez-Mariscal L., Betanzos A., Nava P., and Jaramillo B.E. Tight junction proteins. Prog Biophys Mol Biol 81 (2003) 1-44
39. Staehelin L.A. Further observations on the fine structure of freeze-cleaved tight junctions. J Cell Sci 13 (1973) 763-786
40. Matter K., and Balda M.S. Epithelial tight junctions, gene expression and nucleojunctional interplay. J Cell Sci 120 (2007) 1505-1511
41. Laukoetter M.G., Bruewer M., and Nusrat A. Regulation of the intestinal epithelial barrier by the apical junctional complex. Curr Opin Gastroenterol 22 (2006) 85-89
42. Saitou M., Fujimoto K., Doi Y., Itoh M., Fujimoto T., Furuse M., et al. Occludin-deficient embryonic stem cells can differentiate into polarized epithelial cells bearing tight junctions. J Cell Biol 141 (1998) 397-408
43. Schulzke J.D., Gitter A.H., Mankertz J., Spiegel S., Seidler U., Amasheh S., et al. Epithelial transport and barrier function in occludin-deficient mice. Biochim Biophys Acta 1669 (2005) 34-42
44. Furuse M., Hata M., Furuse K., Yoshida Y., Haratake A., Sugitani Y., et al. Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol 156 (2002) 1099-1111
45. Turksen K., and Troy T.C. Permeability barrier dysfunction in transgenic mice overexpressing claudin 6. Development 129 (2002) 1775-1784
46. Laukoetter M.G., Nava P., Lee W.Y., Severson E.A., Capaldo C.T., Babbin B.A., et al. JAM-A regulates permeability and inflammation in the intestine in vivo. J Exp Med 204 (2007) 3067-3076
47. Madden K.B., Whitman L., Sullivan C., Gause W.C., Urban Jr. J.F., Katona I.M., et al. Role of STAT6 and mast cells in IL-4- and IL-13-induced alterations in murine intestinal epithelial cell function. J Immunol 169 (2002) 4417-4422
48. Madsen K.L., Malfair D., Gray D., Doyle J.S., Jewell L.D., and Fedorak R.N. Interleukin-10 gene-deficient mice develop a primary intestinal permeability defect in response to enteric microflora. Inflamm Bowel Dis 5 (1999) 262-270
49. Arrieta M.C., Madsen K., Doyle J., and Meddings J. Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouse. Gut 58 (2009) 41-48
50. Kuhn R., Lohler J., Rennick D., Rajewsky K., and Muller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75 (1993) 263-274
51. McDermott J.R., Bartram R.E., Knight P.A., Miller H.R., Garrod D.R., and Grencis R.K. Mast cells disrupt epithelial barrier function during enteric nematode infection. Proc Natl Acad Sci U S A 100 (2003) 7761-7766
52. Forbes E.E., Groschwitz K., Abonia J.P., Brandt E.B., Cohen E., Blanchard C., et al. IL-9- and mast cell-mediated intestinal permeability predisposes to oral antigen hypersensitivity. J Exp Med 205 (2008) 897-913
53. Su L., Shen L., Clayburgh D.R., Nalle S.C., Sullivan E.A., Meddings J.B., et al. Targeted epithelial tight junction dysfunction causes immune activation and contributes to development of experimental colitis. Gastroenterology 136 (2009) 551-563
54. Atkinson K.J., and Rao R.K. Role of protein tyrosine phosphorylation in acetaldehyde-induced disruption of epithelial tight junctions. Am J Physiol Gastrointest Liver Physiol 280 (2001) G1280-G1288
55. Seth A., Basuroy S., Sheth P., and Rao R.K. L-Glutamine ameliorates acetaldehyde-induced increase in paracellular permeability in Caco-2 cell monolayer. Am J Physiol Gastrointest Liver Physiol 287 (2004) G510-G517
56. Furuse M., Hirase T., Itoh M., Nagafuchi A., Yonemura S., Tsukita S., et al. Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 123 (1993) 1777-1788
57. Bauer H., Stelzhammer W., Fuchs R., Weiger T.M., Danninger C., Probst G., et al. Astrocytes and neurons express the tight junction-specific protein occludin in vitro. Exp Cell Res 250 (1999) 434-438
58. Barber A.J., Antonetti D.A., and Gardner T.W. Altered expression of retinal occludin and glial fibrillary acidic protein in experimental diabetes. The Penn State Retina Research Group. Invest Ophthalmol Vis Sci 41 (2000) 3561-3568
59. Rescigno M., Urbano M., Valzasina B., Francolini M., Rotta G., Bonasio R., et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2 (2001) 361-367
60. Furuse M., Itoh M., Hirase T., Nagafuchi A., Yonemura S., Tsukita S., et al. Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions. J Cell Biol 127 (1994) 1617-1626
61. Mitic L.L., Van Itallie C.M., and Anderson J.M. Molecular physiology and pathophysiology of tight junctions I. Tight junction structure and function: lessons from mutant animals and proteins. Am J Physiol Gastrointest Liver Physiol 279 (2000) G250-G254
62. Muresan Z., Paul D.L., and Goodenough D.A. Occludin 1B, a variant of the tight junction protein occludin. Mol Biol Cell 11 (2000) 627-634
63. Mankertz J., Waller J.S., Hillenbrand B., Tavalali S., Florian P., Schoneberg T., et al. Gene expression of the tight junction protein occludin includes differential splicing and alternative promoter usage. Biochem Biophys Res Commun 298 (2002) 657-666
64. Balda M.S., Whitney J.A., Flores C., Gonzalez S., Cereijido M., and Matter K. Functional dissociation of paracellular permeability and transepithelial electrical resistance and disruption of the apical-basolateral intramembrane diffusion barrier by expression of a mutant tight junction membrane protein. J Cell Biol 134 (1996) 1031-1049
65. McCarthy K.M., Skare I.B., Stankewich M.C., Furuse M., Tsukita S., Rogers R.A., et al. Occludin is a functional component of the tight junction. J Cell Sci 109 suppl (1996) 2287-2298
66. Wan H., Winton H.L., Soeller C., Tovey E.R., Gruenert D.C., Thompson P.J., et al. Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions. J Clin Invest 104 (1999) 123-133
67. Antonetti D.A., Wolpert E.B., DeMaio L., Harhaj N.S., and Scaduto Jr. R.C. Hydrocortisone decreases retinal endothelial cell water and solute flux coincident with increased content and decreased phosphorylation of occludin. J Neurochem 80 (2002) 667-677
68. Furuse M., Fujimoto K., Sato N., Hirase T., Tsukita S., and Tsukita S. Overexpression of occludin, a tight junction-associated integral membrane protein, induces the formation of intracellular multilamellar bodies bearing tight junction-like structures. J Cell Sci 109 suppl (1996) 429-435
69. Van Itallie C.M., and Anderson J.M. Occludin confers adhesiveness when expressed in fibroblasts. J Cell Sci 110 suppl (1997) 1113-1121
70. Chen M.L., Pothoulakis C., and LaMont J.T. Protein kinase C signaling regulates ZO-1 translocation and increased paracellular flux of T84 colonocytes exposed to Clostridium difficile toxin A. J Biol Chem 277 (2002) 4247-4254
71. Nunbhakdi-Craig V., Machleidt T., Ogris E., Bellotto D., White III C.L., and Sontag E. Protein phosphatase 2A associates with and regulates atypical PKC and the epithelial tight junction complex. J Cell Biol 158 (2002) 967-978
72. Suzuki T., Elias B.C., Seth A., Shen L., Turner J.R., Giorgianni F., et al. PKC eta regulates occludin phosphorylation and epithelial tight junction integrity. Proc Natl Acad Sci U S A 106 (2009) 61-66
73. Harhaj N.S., and Antonetti D.A. Regulation of tight junctions and loss of barrier function in pathophysiology. Int J Biochem Cell Biol 36 (2004) 1206-1237
74. Schneeberger E.E., and Lynch R.D. The tight junction: a multifunctional complex. Am J Physiol Cell Physiol 286 (2004) C1213-C1228
75. Turksen K., and Troy T.C. Barriers built on claudins. J Cell Sci 117 (2004) 2435-2447
76. Morita K., Furuse M., Fujimoto K., and Tsukita S. Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc Natl Acad Sci U S A 96 (1999) 511-516
77. Itoh M., Furuse M., Morita K., Kubota K., Saitou M., and Tsukita S. Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. J Cell Biol 147 (1999) 1351-1363
78. McCarthy K.M., Francis S.A., McCormack J.M., Lai J., Rogers R.A., Skare I.B., et al. Inducible expression of claudin-1-myc but not occludin-VSV-G results in aberrant tight junction strand formation in MDCK cells. J Cell Sci 113 suppl (2000) 3387-3398
79. Furuse M., Fujita K., Hiiragi T., Fujimoto K., and Tsukita S. Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 141 (1998) 1539-1550
80. Ebnet K., Suzuki A., Ohno S., and Vestweber D. Junctional adhesion molecules (JAMs): more molecules with dual functions?. J Cell Sci 117 (2004) 19-29
81. Bazzoni G. The JAM family of junctional adhesion molecules. Curr Opin Cell Biol 15 (2003) 525-530
82. Williams L.A., Martin-Padura I., Dejana E., Hogg N., and Simmons D.L. Identification and characterisation of human junctional adhesion molecule (JAM). Mol Immunol 36 (1999) 1175-1188
83. Liu Y., Nusrat A., Schnell F.J., Reaves T.A., Walsh S., Pochet M., et al. Human junction adhesion molecule regulates tight junction resealing in epithelia. J Cell Sci 113 suppl (2000) 2363-2374
84. Bazzoni G., Martinez-Estrada O.M., Mueller F., Nelboeck P., Schmid G., Bartfai T., et al. Homophilic interaction of junctional adhesion molecule. J Biol Chem 275 (2000) 30970-30976
85. Babinska A., Kedees M.H., Athar H., Sobocki T., Sobocka M.B., Ahmed T., et al. Two regions of the human platelet F11-receptor (F11R) are critical for platelet aggregation, potentiation and adhesion. Thromb Haemost 87 (2002) 712-721
86. Krause G., Winkler L., Mueller S.L., Haseloff R.F., Piontek J., and Blasig I.E. Structure and function of claudins. Biochim Biophys Acta 1778 (2008) 631-645
87. Furuse M., Sasaki H., and Tsukita S. Manner of interaction of heterogeneous claudin species within and between tight junction strands. J Cell Biol 147 (1999) 891-903
88. Furuse M., Furuse K., Sasaki H., and Tsukita S. Conversion of zonulae occludentes from tight to leaky strand type by introducing claudin-2 into Madin-Darby canine kidney I cells. J Cell Biol 153 (2001) 263-272
89. Yu A.S., Enck A.H., Lencer W.I., and Schneeberger E.E. Claudin-8 expression in Madin-Darby canine kidney cells augments the paracellular barrier to cation permeation. J Biol Chem 278 (2003) 17350-17359
90. Colegio O.R., Van Itallie C., Rahner C., and Anderson J.M. Claudin extracellular domains determine paracellular charge selectivity and resistance but not tight junction fibril architecture. Am J Physiol Cell Physiol 284 (2003) C1346-C1354
91. Colegio O.R., Van Itallie C.M., McCrea H.J., Rahner C., and Anderson J.M. Claudins create charge-selective channels in the paracellular pathway between epithelial cells. Am J Physiol Cell Physiol 283 (2002) C142-C147
92. Van Itallie C.M., Holmes J., Bridges A., Gookin J.L., Coccaro M.R., Proctor W., et al. The density of small tight junction pores varies among cell types and is increased by expression of claudin-2. J Cell Sci 121 (2008) 298-305
93. Agarwal R., D'Souza T., and Morin P.J. Claudin-3 and claudin-4 expression in ovarian epithelial cells enhances invasion and is associated with increased matrix metalloproteinase-2 activity. Cancer Res 65 (2005) 7378-7385
94. D'Souza T., Agarwal R., and Morin P.J. Phosphorylation of claudin-3 at threonine 192 by cAMP-dependent protein kinase regulates tight junction barrier function in ovarian cancer cells. J Biol Chem 280 (2005) 26233-26240
95. D'Souza T., Indig F.E., and Morin P.J. Phosphorylation of claudin-4 by PKCepsilon regulates tight junction barrier function in ovarian cancer cells. Exp Cell Res 313 (2007) 3364-3375
96. Yamauchi K., Rai T., Kobayashi K., Sohara E., Suzuki T., Itoh T., et al. Disease-causing mutant WNK4 increases paracellular chloride permeability and phosphorylates claudins. Proc Natl Acad Sci U S A 101 (2004) 4690-4694
97. Gonzalez-Mariscal L., Tapia R., and Chamorro D. Crosstalk of tight junction components with signaling pathways. Biochim Biophys Acta 1778 (2008) 729-756
98. Fujibe M., Chiba H., Kojima T., Soma T., Wada T., Yamashita T., et al. Thr203 of claudin-1, a putative phosphorylation site for MAP kinase, is required to promote the barrier function of tight junctions. Exp Cell Res 295 (2004) 36-47
99. Roh M.H., Liu C.J., Laurinec S., and Margolis B. The carboxyl terminus of zona occludens-3 binds and recruits a mammalian homologue of discs lost to tight junctions. J Biol Chem 277 (2002) 27501-27509
100. Aijaz S., Balda M.S., and Matter K. Tight junctions: molecular architecture and function. Int Rev Cytol 248 (2006) 261-298
101. Macara I.G. Parsing the polarity code. Nat Rev Mol Cell Biol 5 (2004) 220-231
102. Van Itallie C.M., Rogan S., Yu A., Vidal L.S., Holmes J., and Anderson J.M. Two splice variants of claudin-10 in the kidney create paracellular pores with different ion selectivities. Am J Physiol Renal Physiol 291 (2006) F1288-F1299
103. Meddings J.B., Jarand J., Urbanski S.J., Hardin J., and Gall D.G. Increased gastrointestinal permeability is an early lesion in the spontaneously diabetic BB rat. Am J Physiol Gastrointest Liver Physiol 276 (1999) G951-G957
104. MacDonald T.T., Hutchings P., Choy M.Y., Murch S., and Cooke A. Tumour necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflamed human intestine. Clin Exp Immunol 81 (1990) 301-305
105. Fais S., Capobianchi M.R., Silvestri M., Mercuri F., Pallone F., and Dianzani F. Interferon expression in Crohn's disease patients: increased interferon-gamma and -alpha mRNA in the intestinal lamina propria mononuclear cells. J Interferon Res 14 (1994) 235-238
106. Ye D., Ma I., and Ma T.Y. Molecular mechanism of tumor necrosis factor-alpha modulation of intestinal epithelial tight junction barrier. Am J Physiol Gastrointest Liver Physiol 290 (2006) G496-G504
107. Zolotarevsky Y., Hecht G., Koutsouris A., Gonzalez D.E., Quan C., Tom J., et al. A membrane-permeant peptide that inhibits MLC kinase restores barrier function in in vitro models of intestinal disease. Gastroenterology 123 (2002) 163-172
108. Mankertz J., Tavalali S., Schmitz H., Mankertz A., Riecken E.O., Fromm M., et al. Expression from the human occludin promoter is affected by tumor necrosis factor alpha and interferon gamma. J Cell Sci 113 suppl (2000) 2085-2090
109. Zund G., Madara J.L., Dzus A.L., Awtrey C.S., and Colgan S.P. Interleukin-4 and interleukin-13 differentially regulate epithelial chloride secretion. J Biol Chem 271 (1996) 7460-7464
110. Ceponis P.J., Botelho F., Richards C.D., and McKay D.M. Interleukins 4 and 13 increase intestinal epithelial permeability by a phosphatidylinositol 3-kinase pathway. Lack of evidence for STAT 6 involvement. J Biol Chem 275 (2000) 29132-29137
111. Berin M.C., Yang P.C., Ciok L., Waserman S., and Perdue M.H. Role for IL-4 in macromolecular transport across human intestinal epithelium. Am J Physiol Cell Physiol 276 (1999) C1046-C1052
112. Prasad S., Mingrino R., Kaukinen K., Hayes K.L., Powell R.M., MacDonald T.T., et al. Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells. Lab Invest 85 (2005) 1139-1162
113. Madsen K.L., Tavernini M.M., Mosmann T.R., and Fedorak R.N. Interleukin 10 modulates ion transport in rat small intestine. Gastroenterology 111 (1996) 936-944
114. Madsen K.L., Lewis S.A., Tavernini M.M., Hibbard J., and Fedorak R.N. Interleukin 10 prevents cytokine-induced disruption of T84 monolayer barrier integrity and limits chloride secretion. Gastroenterology 113 (1997) 151-159
115. Fasano A., and Shea-Donohue T. Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal diseases. Nat Clin Pract Gastroenterol Hepatol 2 (2005) 416-422
116. Musch M.W., Clarke L.L., Mamah D., Gawenis L.R., Zhang Z., Ellsworth W., et al. T cell activation causes diarrhea by increasing intestinal permeability and inhibiting epithelial Na+/K+-ATPase. J Clin Invest 110 (2002) 1739-1747
117. Clayburgh D.R., Barrett T.A., Tang Y., Meddings J.B., Van Eldik L.J., Watterson D.M., et al. Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo. J Clin Invest 115 (2005) 2702-2715
118. Clayburgh D.R., Musch M.W., Leitges M., Fu Y.X., and Turner J.R. Coordinated epithelial NHE3 inhibition and barrier dysfunction are required for TNF-mediated diarrhea in vivo. J Clin Invest 116 (2006) 2682-2694
119. Dalton J.E., Cruickshank S.M., Egan C.E., Mears R., Newton D.J., Andrew E.M., et al. Intraepithelial gammadelta+ lymphocytes maintain the integrity of intestinal epithelial tight junctions in response to infection. Gastroenterology 131 (2006) 818-829
120. Yu L.C., and Perdue M.H. Role of mast cells in intestinal mucosal function: studies in models of hypersensitivity and stress. Immunol Rev 179 (2001) 61-73
121. Galli S.J., Grimbaldeston M., and Tsai M. Immunomodulatory mast cells: negative, as well as positive, regulators of immunity. Nat Rev Immunol 8 (2008) 478-486
122. Bischoff S.C., and Kramer S. Human mast cells, bacteria, and intestinal immunity. Immunol Rev 217 (2007) 329-337
123. Bischoff S.C. Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data. Nat Rev Immunol 7 (2007) 93-104
124. Pennock J.L., and Grencis R.K. The mast cell and gut nematodes: damage and defence. Chem Immunol Allergy 90 (2006) 128-140
125. Crowe S.E., Soda K., Stanisz A.M., and Perdue M.H. Intestinal permeability in allergic rats: nerve involvement in antigen-induced changes. Am J Physiol Gastrointest Liver Physiol 264 (1993) G617-G6123
126. Perdue M.H., Masson S., Wershil B.K., and Galli S.J. Role of mast cells in ion transport abnormalities associated with intestinal anaphylaxis. Correction of the diminished secretory response in genetically mast cell-deficient W/Wv mice by bone marrow transplantation. J Clin Invest 87 (1991) 687-693
127. Berin M.C., Kiliaan A.J., Yang P.C., Groot J.A., Taminiau J.A., and Perdue M.H. Rapid transepithelial antigen transport in rat jejunum: impact of sensitization and the hypersensitivity reaction. Gastroenterology 113 (1997) 856-864
128. Crowe S.E., Sestini P., and Perdue M.H. Allergic reactions of rat jejunal mucosa. Ion transport responses to luminal antigen and inflammatory mediators. Gastroenterology 99 (1990) 74-82
129. Jeziorska M., Haboubi N., Schofield P., and Woolley D.E. Distribution and activation of eosinophils in inflammatory bowel disease using an improved immunohistochemical technique. J Pathol 194 (2001) 484-492
130. Levy A.M., Gleich G.J., Sandborn W.J., Tremaine W.J., Steiner B.L., and Phillips S.F. Increased eosinophil granule proteins in gut lavage fluid from patients with inflammatory bowel disease. Mayo Clin Proc 72 (1997) 117-123
131. Carvalho A.T., Elia C.C., de Souza H.S., Elias P.R., Pontes E.L., Lukashok H.P., et al. Immunohistochemical study of intestinal eosinophils in inflammatory bowel disease. J Clin Gastroenterol 36 (2003) 120-125
132. Laukoetter M.G., Nava P., and Nusrat A. Role of the intestinal barrier in inflammatory bowel disease. World J Gastroenterol 14 (2008) 401-407
133. Furuta G.T., Nieuwenhuis E.E., Karhausen J., Gleich G., Blumberg R.S., Lee J.J., et al. Eosinophils alter colonic epithelial barrier function: role for major basic protein. Am J Physiol Gastrointest Liver Physiol 289 (2005) G890-G897
134. Bode J.C. Alcohol and the gastrointestinal tract. Ergeb Inn Med Kinderheilkd 45 (1980) 1-75
135. Beck I.T., and Dinda P.K. Acute exposure of small intestine to ethanol: effects on morphology and function. Dig Dis Sci 26 (1981) 817-838
136. Ferrier L., Berard F., Debrauwer L., Chabo C., Langella P., Bueno L., et al. Impairment of the intestinal barrier by ethanol involves enteric microflora and mast cell activation in rodents. Am J Pathol 168 (2006) 1148-1154
137. Banan A., Fields J.Z., Decker H., Zhang Y., and Keshavarzian A. Nitric oxide and its metabolites mediate ethanol-induced microtubule disruption and intestinal barrier dysfunction. J Pharmacol Exp Ther 294 (2000) 997-1008
138. Lambert J.C., Zhou Z., Wang L., Song Z., McClain C.J., and Kang Y.J. Prevention of alterations in intestinal permeability is involved in zinc inhibition of acute ethanol-induced liver damage in mice. J Pharmacol Exp Ther 305 (2003) 880-886
139. Barona E., Pirola R.C., and Leiber C.S. Small intestinal damage and changes in cell population produced by ethanol ingestion in the rat. Gastroenterology 66 (1974) 226-234
140. Shibayama Y., Asaka S., and Nakata K. Endotoxin hepatotoxicity augmented by ethanol. Exp Mol Pathol 55 (1991) 196-202
141. Tamai H., Horie Y., Kato S., Yokoyama H., and Ishii H. Long-term ethanol feeding enhances susceptibility of the liver to orally administered lipopolysaccharides in rats. Alcohol Clin Exp Res 26 suppl (2002) 75S-80S
142. Gottfried E.B., Korsten M.A., and Lieber C.S. Alcohol-induced gastric and duodenal lesions in man. Am J Gastroenterol 70 (1978) 587-592
143. Parlesak A., Schafer C., Schutz T., Bode J.C., and Bode C. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. J Hepatol 32 (2000) 742-747
144. Dinda P.K., Leddin D.J., and Beck I.T. Histamine is involved in ethanol-induced jejunal microvascular injury in rabbits. Gastroenterology 95 (1988) 1227-1233
145. Dinda P.K., Kossev P., Beck I.T., and Buell M.G. Role of xanthine oxidase-derived oxidants and leukocytes in ethanol-induced jejunal mucosal injury. Dig Dis Sci 41 (1996) 2461-2470
146. Robert A. An intestinal disease produced experimentally by a prostaglandin deficiency. Gastroenterology 69 (1975) 1045-1047
147. Whittle B.J. Temporal relationship between cyclooxygenase inhibition, as measured by prostacyclin biosynthesis, and the gastrointestinal damage induced by indomethacin in the rat. Gastroenterology 80 (1981) 94-98
148. Bjarnason I., Zanelli G., Smith T., Prouse P., Williams P., Smethurst P., et al. Nonsteroidal antiinflammatory drug-induced intestinal inflammation in humans. Gastroenterology 93 (1987) 480-489
149. Kaufmann H.J., and Taubin H.L. Nonsteroidal anti-inflammatory drugs activate quiescent inflammatory bowel disease. Ann Intern Med 107 (1987) 513-516
150. Fries J.F., Miller S.R., Spitz P.W., Williams C.A., Hubert H.B., and Bloch D.A. Toward an epidemiology of gastropathy associated with nonsteroidal antiinflammatory drug use. Gastroenterology 96 (1989) 647-655
151. Lanas A., Sekar M.C., and Hirschowitz B.I. Objective evidence of aspirin use in both ulcer and nonulcer upper and lower gastrointestinal bleeding. Gastroenterology 103 (1992) 862-869
152. Langman M.J., Weil J., Wainwright P., Lawson D.H., Rawlins M.D., Logan R.F., et al. Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Lancet 343 (1994) 1075-1078
153. Lanas A., Serrano P., Bajador E., Esteva F., Benito R., and Sainz R. Evidence of aspirin use in both upper and lower gastrointestinal perforation. Gastroenterology 112 (1997) 683-689
154. Sigthorsson G., Jacob M., Wrigglesworth J., Somasundaram S., Tavares I., Foster R., et al. Comparison of indomethacin and nimesulide, a selective cyclooxygenase-2 inhibitor, on key pathophysiologic steps in the pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in the rat. Scand J Gastroenterol 33 (1998) 728-735
155. Sigthorsson G., Tibble J., Hayllar J., Menzies I., Macpherson A., Moots R., et al. Intestinal permeability and inflammation in patients on NSAIDs. Gut 43 (1998) 506-511
156. Oshima T., Miwa H., and Joh T. Aspirin induces gastric epithelial barrier dysfunction by activating p38 MAPK via claudin-7. Am J Physiol Cell Physiol 295 (2008) C800-C806
157. Meyer R.A., McGinley D., and Posalaky Z. The effects of 16,16-dimethyl prostaglandin E2 + aspirin on the canine gastric mucosal barrier. Virchows Arch A Pathol Anat Histopathol 412 (1987) 119-125
158. Wallace J.L., Keenan C.M., and Granger D.N. Gastric ulceration induced by nonsteroidal anti-inflammatory drugs is a neutrophil-dependent process. Am J Physiol Gatrointest Liver Physiol 259 (1990) G462-G467
159. Takeuchi K., Ueshima K., Hironaka Y., Fujioka Y., Matsumoto J., and Okabe S. Oxygen free radicals and lipid peroxidation in the pathogenesis of gastric mucosal lesions induced by indomethacin in rats. Relation to gastric hypermotility. Digestion 49 (1991) 175-184
160. Tanaka A., Kunikata T., Mizoguchi H., Kato S., and Takeuchi K. Dual action of nitric oxide in pathogenesis of indomethacin-induced small intestinal ulceration in rats. J Physiol Pharmacol 50 (1999) 405-417
161. Somasundaram S., Sigthorsson G., Simpson R.J., Watts J., Jacob M., Tavares I.A., et al. Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat. Aliment Pharmacol Ther 14 (2000) 639-650
162. Berkes J., Viswanathan V.K., Savkovic S.D., and Hecht G. Intestinal epithelial responses to enteric pathogens: effects on the tight junction barrier, ion transport, and inflammation. Gut 52 (2003) 439-451
163. Wu Z., Milton D., Nybom P., Sjo A., and Magnusson K.E. Vibrio cholerae hemagglutinin/protease (HA/protease) causes morphological changes in cultured epithelial cells and perturbs their paracellular barrier function. Microb Pathog 21 (1996) 111-123
164. Mel S.F., Fullner K.J., Wimer-Mackin S., Lencer W.I., and Mekalanos J.J. Association of protease activity in Vibrio cholerae vaccine strains with decreases in transcellular epithelial resistance of polarized T84 intestinal epithelial cells. Infect Immun 68 (2000) 6487-6492
165. Wu Z., Nybom P., and Magnusson K.E. Distinct effects of Vibrio cholerae haemagglutinin/protease on the structure and localization of the tight junction-associated proteins occludin and ZO-1. Cell Microbiol 2 (2000) 11-17
166. Fasano A., Baudry B., Pumplin D.W., Wasserman S.S., Tall B.D., Ketley J.M., et al. Vibrio cholerae produces a second enterotoxin, which affects intestinal tight junctions. Proc Natl Acad Sci U S A 88 (1991) 5242-5246
167. Fasano A., Fiorentini C., Donelli G., Uzzau S., Kaper J.B., Margaretten K., et al. Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro. J Clin Invest 96 (1995) 710-720
168. Schmidt E., Kelly S.M., and van der Walle C.F. Tight junction modulation and biochemical characterisation of the zonula occludens toxin C- and N-termini. FEBS Lett 581 (2007) 2974-2980
169. Fasano A., Uzzau S., Fiore C., and Margaretten K. The enterotoxic effect of zonula occludens toxin on rabbit small intestine involves the paracellular pathway. Gastroenterology 112 (1997) 839-846
170. Wang W., Uzzau S., Goldblum S.E., and Fasano A. Human zonulin, a potential modulator of intestinal tight junctions. J Cell Sci 113 suppl (2000) 4435-4440
171. Knutton S., Lloyd D.R., and McNeish A.S. Adhesion of enteropathogenic Escherichia coli to human intestinal enterocytes and cultured human intestinal mucosa. Infect Immun 55 (1987) 69-77
172. Jarvis K.G., Giron J.A., Jerse A.E., McDaniel T.K., Donnenberg M.S., and Kaper J.B. Enteropathogenic Escherichia coli contains a putative type III secretion system necessary for the export of proteins involved in attaching and effacing lesion formation. Proc Natl Acad Sci U S A 92 (1995) 7996-8000
173. Spitz J., Yuhan R., Koutsouris A., Blatt C., Alverdy J., and Hecht G. Enteropathogenic Escherichia coli adherence to intestinal epithelial monolayers diminishes barrier function. Am J Physiol Gastrointest Liver Physiol 268 (1995) G374-G379
174. Muza-Moons M.M., Schneeberger E.E., and Hecht G.A. Enteropathogenic Escherichia coli infection leads to appearance of aberrant tight junctions strands in the lateral membrane of intestinal epithelial cells. Cell Microbiol 6 (2004) 783-793
175. Philpott D.J., McKay D.M., Sherman P.M., and Perdue M.H. Infection of T84 cells with enteropathogenic Escherichia coli alters barrier and transport functions. Am J Physiol Gastrointest Liver Physiol 270 (1996) G634-G645
176. Yuhan R., Koutsouris A., Savkovic S.D., and Hecht G. Enteropathogenic Escherichia coli-induced myosin light chain phosphorylation alters intestinal epithelial permeability. Gastroenterology 113 (1997) 1873-1882
177. Fujita K., Katahira J., Horiguchi Y., Sonoda N., Furuse M., and Tsukita S. Clostridium perfringens enterotoxin binds to the second extracellular loop of claudin-3, a tight junction integral membrane protein. FEBS Lett 476 (2000) 258-261
178. Katahira J., Sugiyama H., Inoue N., Horiguchi Y., Matsuda M., and Sugimoto N. Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo. J Biol Chem 272 (1997) 26652-26658
179. Singh U., Mitic L.L., Wieckowski E.U., Anderson J.M., and McClane B.A. Comparative biochemical and immunocytochemical studies reveal differences in the effects of Clostridium perfringens enterotoxin on polarized CaCo-2 cells versus Vero cells. J Biol Chem 276 (2001) 33402-33412
180. Singh U., Van Itallie C.M., Mitic L.L., Anderson J.M., and McClane B.A. CaCo-2 cells treated with Clostridium perfringens enterotoxin form multiple large complex species, one of which contains the tight junction protein occludin. J Biol Chem 275 (2000) 18407-18417
181. Sonoda N., Furuse M., Sasaki H., Yonemura S., Katahira J., Horiguchi Y., et al. Clostridium perfringens enterotoxin fragment removes specific claudins from tight junction strands: Evidence for direct involvement of claudins in tight junction barrier. J Cell Biol 147 (1999) 195-204
182. Chakrabarti G., and McClane B.A. The importance of calcium influx, calpain and calmodulin for the activation of CaCo-2 cell death pathways by Clostridium perfringens enterotoxin. Cell Microbiol 7 (2005) 129-146
183. Chakrabarti G., Zhou X., and McClane B.A. Death pathways activated in CaCo-2 cells by Clostridium perfringens enterotoxin. Infect Immun 71 (2003) 4260-4270
184. Meddings J. The significance of the gut barrier in disease. Gut 57 (2008) 438-440
185. Buhner S., Buning C., Genschel J., Kling K., Herrmann D., Dignass A., et al. Genetic basis for increased intestinal permeability in families with Crohn's disease: role of CARD15 3020insC mutation?. Gut 55 (2006) 342-347
186. Takeuchi K., Maiden L., and Bjarnason I. Genetic aspects of intestinal permeability in inflammatory bowel disease. In: Chadwick D., and Goode J. (Eds). Inflammatory bowel disease-crossroads of microbes, epithelium and immune systems (2004), Wiley, Chichester 151-163
187. Mankertz J., and Schulzke J. Altered permeability in inflammatory bowel disease: pathophysiology and clinical implications. Curr Opin Gastroenterol 23 (2007) 379-383
188. Heyman M., and Desjeux J.F. Cytokine-induced alteration of the epithelial barrier to food antigens in disease. Ann N Y Acad Sci 202 (2003) 304-311
189. Heymann M. Gut barrier dysfunction in food allergy. Eur J Gastroenterol Hepatol 17 (2005) 1279-1285
190. Andre C., Andre F., Colin L., and Cavagna S. Measurement of intestinal permeability to mannitol and lactulose as a means of diagnosing food allergy and evaluating therapeutic effectiveness of disodium cromoglycate. Ann Allergy 59 (1987) 127-130
191. Baert F.J., D'Haens G.R., Peeters M., Hiele M.I., Schaible T.F., Shealy D., et al. Tumor necrosis factor alpha antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileocolitis. Gastroenterology 116 (1999) 22-28
192. Suenaert P., Bulteel V., Lemmens L., Noman M., Geypens B., Van Assche G., et al. Anti-tumor necrosis factor treatment restores the gut barrier in Crohn's disease. Am J Gastroenterol 97 (2002) 2000-2004
193. Drago S., El Asmar R., Di Pierro M., Grazia Clemente M., Tripathi A., Sapone A., et al. Gliadin, zonulin and gut permeability: effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol 41 (2006) 408-419
194. Fasano A., Not T., Wang W., Uzzau S., Berti I., Tommasini A., et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet 355 (2000) 1518-1519
195. Watts T., Berti I., Sapone A., Gerarduzzi T., Not T., Zielke R., et al. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci U S A 102 (2005) 2916-2921
196. Sapone A., de Magistris L., Pietzak M., Clemente M.G., Tripathi A., Cucca F., et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes 55 (2006) 1443-1449
197. Mazzon E., Sturniolo G.C., Puzzolo D., Frisina N., and Fries W. Effect of stress on the paracellular barrier in the rat ileum. Gut 51 (2002) 507-513
198. Santos J., Saunders P.R., Hanssen N.P., Yang P.C., Yates D., Groot J.A., et al. Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat. Am J Physiol Gastrointest Liver Physiol 277 (1999) G391-G399
199. Santos J., Bayarri C., Saperas E., Nogueiras C., Antolin M., Mourelle M., et al. Characterisation of immune mediator release during the immediate response to segmental mucosal challenge in the jejunum of patients with food allergy. Gut 45 (1999) 553-558
200. Santos J., Benjamin M., Yang P.C., Prior T., and Perdue M.H. Chronic stress impairs rat growth and jejunal epithelial barrier function: role of mast cells. Am J Physiol Gastrointest Liver Physiol 278 (2000) G847-G854
201. Castagliuolo I., Wershil B.K., Karalis K., Pasha A., Nikulasson S.T., and Pothoulakis C. Colonic mucin release in response to immobilization stress is mast cell dependent. Am J Physiol Gastrointest Liver Physiol 274 (1998) G1094-G1100
202. Bjarnason I., and Peters T.J. In vitro determination of small intestinal permeability: demonstration of a persistent defect in patients with coeliac disease. Gut 25 (1984) 145-150
203. Schulzke J.D., Bentzel C.J., Schulzke I., Riecken E.O., and Fromm M. Epithelial tight junction structure in the jejunum of children with acute and treated celiac sprue. Pediatr Res 43 (1998) 435-441
204. Wyatt J., Vogelsang H., Hubl W., Waldhoer T., and Lochs H. Intestinal permeability and the prediction of relapse in Crohn's disease. Lancet 341 (1993) 1437-1439
205. D'Inca R., Di Leo V., Corrao G., Martines D., D'Odorico A., Mestriner C., et al. Intestinal permeability test as a predictor of clinical course in Crohn's disease. Am J Gastroenterol 94 (1999) 2956-2960
206. Ventura M.T., Polimeno L., Amoruso A.C., Gatti F., Annoscia E., Marinaro M., et al. Intestinal permeability in patients with adverse reactions to food. Dig Liver Dis 38 (2006) 732-736
207. Laudat A., Arnaud P., Napoly A., and Brion F. The intestinal permeability test applied to the diagnosis of food allergy in pediatrics. West Indian Med J 43 (1994) 87-88
208. Lacaille F., Laurent J., and Bousquet J. Life-threatening food allergy in a child treated with FK506. J Pediatr Gastroenterol Nutr 25 (1997) 228-229
209. Asante-Korang A., Boyle G.J., Webber S.A., Miller S.A., and Fricker F.J. Experience of FK506 immune suppression in pediatric heart transplantation: a study of long-term adverse effects. J Heart Lung Transplant 15 (1996) 415-422
210. Granot E., Yakobovich E., and Bardenstein R. Tacrolimus immunosuppression-an association with asymptomatic eosinophilia and elevated total and specific IgE levels. Pediatr Transplant 10 (2006) 690-693
211. Fisher A., Schwartz M., Mor E., Sheiner P., Emre S., Guy S., et al. Gastrointestinal toxicity associated with FK 506 in liver transplant recipients. Transplant Proc 26 (1994) 3106-3107
212. Gabe S.M., Bjarnason I., Tolou-Ghamari Z., Tredger J.M., Johnson P.G., Barclay G.R., et al. The effect of tacrolimus (FK506) on intestinal barrier function and cellular energy production in humans. Gastroenterology 115 (1998) 67-74
213. Boyle R.J., Hardikar W., and Tang M.L. The development of food allergy after liver transplantation. Liver Transpl 11 (2005) 326-330
214. Legendre C., Caillat-Zucman S., Samuel D., Morelon S., Bismuth H., Bach J.F., et al. Transfer of symptomatic peanut allergy to the recipient of a combined liver-and-kidney transplant. N Engl J Med 337 (1997) 822-824
215. Chehade M., Nowak-Wegrzyn A., Kaufman S.S., Fishbein T.M., Tschernia A., and LeLeiko N.S. De novo food allergy after intestinal transplantation: a report of three cases. J Pediatr Gastroenterol Nutr 38 (2004) 545-547
216. Ozdemir O., Arrey-Mensah A., and Sorensen R.U. Development of multiple food allergies in children taking tacrolimus after heart and liver transplantation. Pediatr Transplant 10 (2006) 380-383
217. Madsen K.L., Yanchar N.L., Sigalet D.L., Reigel T., and Fedorak R.N. FK506 increases permeability in rat intestine by inhibiting mitochondrial function. Gastroenterology 109 (1995) 107-114
218. Madara J.L., Parkos C., Colgan S., Nusrat A., Atisook K., and Kaoutzani P. The movement of solutes and cells across tight junctions. Ann N Y Acad Sci 664 (1992) 47-60
219. Liu J., Farmer Jr. J.D., Lane W.S., Friedman J., Weissman I., and Schreiber S.L. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 66 (1991) 807-815
220. Hall E.J., and Batt R.M. Abnormal permeability precedes the development of a gluten sensitive enteropathy in Irish setter dogs. Gut 32 (1991) 749-753
221. Li X.M., Schofield B.H., Huang C.K., Kleiner G.I., and Sampson H.A. A murine model of IgE-mediated cow's milk hypersensitivity. J Allergy Clin Immunol 103 (1999) 206-214
222. Brandt E.B., Strait R.T., Hershko D., Wang Q., Muntel E.E., Scribner T.A., et al. Mast cells are required for experimental oral allergen-induced diarrhea. J Clin Invest 112 (2003) 1666-1677
223. Berin M.C., Kiliaan A.J., Yang P.C., Groot J.A., Kitamura Y., and Perdue M.H. The influence of mast cells on pathways of transepithelial antigen transport in rat intestine. J Immunol 161 (1998) 2561-2566
224. Clayburgh D.R., Shen L., and Turner J.R. A porous defense: the leaky epithelial barrier in intestinal disease. Lab Invest 84 (2004) 282-291
225. Secondulfo M., de Magistris L., Fiandra R., Caserta L., Belletta M., Tartaglione M.T., et al. Intestinal permeability in Crohn's disease patients and their first degree relatives. Dig Liver Dis 33 (2001) 680-685
226. Soderholm J.D., Olaison G., Lindberg E., Hannestad U., Vindels A., Tysk C., et al. Different intestinal permeability patterns in relatives and spouses of patients with Crohn's disease: an inherited defect in mucosal defence?. Gut 44 (1999) 96-100
227. Peeters M., Geypens B., Claus D., Nevens H., Ghoos Y., Verbeke G., et al. Clustering of increased small intestinal permeability in families with Crohn's disease. Gastroenterology 113 (1997) 802-807
228. Hilsden R.J., Meddings J.B., and Sutherland L.R. Intestinal permeability changes in response to acetylsalicylic acid in relatives of patients with Crohn's disease. Gastroenterology 110 (1996) 1395-1403
229. Irvine E.J., and Marshall J.K. Increased intestinal permeability precedes the onset of Crohn's disease in a subject with familial risk. Gastroenterology 119 (2000) 1740-1744
230. Olson T.S., Reuter B.K., Scott K.G., Morris M.A., Wang X.M., Hancock L.N., et al. The primary defect in experimental ileitis originates from a nonhematopoietic source. J Exp Med 203 (2006) 541-552
231. Resta-Lenert S., Smitham J., and Barrett K.E. Epithelial dysfunction associated with the development of colitis in conventionally housed mdr1a-/- mice. Am J Physiol Gastrointest Liver Physiol 289 (2005) G153-G162
232. Hugot J.P., Chamaillard M., Zouali H., Lesage S., Cezard J.P., Belaiche J., et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411 (2001) 599-603
233. Ogura Y., Bonen D.K., Inohara N., Nicolae D.L., Chen F.F., Ramos R., et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411 (2001) 603-606
234. Gitter A.H., Bendfeldt K., Schulzke J.D., and Fromm M. Leaks in the epithelial barrier caused by spontaneous and TNF-alpha-induced single-cell apoptosis. FASEB J 14 (2000) 1749-1753
235. Kucharzik T., Walsh S.V., Chen J., Parkos C.A., and Nusrat A. Neutrophil transmigration in inflammatory bowel disease is associated with differential expression of epithelial intercellular junction proteins. Am J Pathol 159 (2001) 2001-2009
236. Zeissig S., Burgel N., Gunzel D., Richter J., Mankertz J., Wahnschaffe U., et al. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Gut 56 (2007) 61-72
237. Madara J.L., and Stafford J. Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers. J Clin Invest 83 (1989) 724-727
238. Mullin J.M., Laughlin K.V., Marano C.W., Russo L.M., and Soler A.P. Modulation of tumor necrosis factor-induced increase in renal (LLC-PK1) transepithelial permeability. Am J Physiol 263 (1992) F915-F924
239. Madara J.L., and Trier J.S. Structural abnormalities of jejunal epithelial cell membranes in celiac sprue. Lab Invest 43 (1980) 254-261
240. Smecuol E., Bai J.C., Vazquez H., Kogan Z., Cabanne A., Niveloni S., et al. Gastrointestinal permeability in celiac disease. Gastroenterology 112 (1997) 1129-1136
241. van Elburg R.M., Uil J.J., Mulder C.J., and Heymans H.S. Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease. Gut 34 (1993) 354-357
242. Batt R.M., Carter M.W., and McLean L. Morphological and biochemical studies of a naturally occurring enteropathy in the Irish setter dog: a comparison with coeliac disease in man. Res Vet Sci 37 (1984) 339-346
243. Lammers K.M., Lu R., Brownley J., Lu B., Gerard C., Thomas K., et al. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology 135 (2008) 194-204 e3
244. Clemente M.G., De Virgiliis S., Kang J.S., Macatagney R., Musu M.P., Di Pierro M.R., et al. Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut 52 (2003) 218-223
245. Montalto M., Cuoco L., Ricci R., Maggiano N., Vecchio F.M., and Gasbarrini G. Immunohistochemical analysis of ZO-1 in the duodenal mucosa of patients with untreated and treated celiac disease. Digestion 65 (2002) 227-233
246. Pizzuti D., Bortolami M., Mazzon E., Buda A., Guariso G., D'Odorico A., et al. Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten-free diet. Dig Liver Dis 36 (2004) 337-341
247. Wolters V.M., and Wijmenga C. Genetic background of celiac disease and its clinical implications. Am J Gastroenterol 103 (2008) 190-195
248. Mooradian A.D., Morley J.E., Levine A.S., Prigge W.F., and Gebhard R.L. Abnormal intestinal permeability to sugars in diabetes mellitus. Diabetologia 29 (1986) 221-224
249. Carratu R., Secondulfo M., de Magistris L., Iafusco D., Urio A., Carbone M.G., et al. Altered intestinal permeability to mannitol in diabetes mellitus type I. J Pediatr Gastroenterol Nutr 28 (1999) 264-269
250. Secondulfo M., Riegler G., De Magistris L., Belletta M., Fiandra R., Caserta L., et al. Intestinal permeability assessment before and after ileal pouch-anal anastomosis. Minerva Gastroenterol Dietol 50 (2004) 155-163
251. Secondulfo M., Iafusco D., Carratu R., deMagistris L., Sapone A., Generoso M., et al. Ultrastructural mucosal alterations and increased intestinal permeability in non-celiac, type I diabetic patients. Dig Liver Dis 36 (2004) 35-45
252. Neu J., Reverte C.M., Mackey A.D., Liboni K., Tuhacek-Tenace L.M., Hatch M., et al. Changes in intestinal morphology and permeability in the biobreeding rat before the onset of type 1 diabetes. J Pediatr Gastroenterol Nutr 40 (2005) 589-595
253. Saunders P.R., Kosecka U., McKay D.M., and Perdue M.H. Acute stressors stimulate ion secretion and increase epithelial permeability in rat intestine. Am J Physiol Gastrointest Liver Physiol 267 (1994) G794-G799
254. Kiliaan A.J., Saunders P.R., Bijlsma P.B., Berin M.C., Taminiau J.A., Groot J.A., et al. Stress stimulates transepithelial macromolecular uptake in rat jejunum. Am J Physiol Gastrointest Liver Physiol 275 (1998) G1037-G1044
255. Levenstein S., Prantera C., Varvo V., Scribano M.L., Andreoli A., Luzi C., et al. Stress and exacerbation in ulcerative colitis: a prospective study of patients enrolled in remission. Am J Gastroenterol 95 (2000) 1213-1220
256. Collins S.M. Stress and the gastrointestinal tract IV. Modulation of intestinal inflammation by stress: basic mechanisms and clinical relevance. Am J Physiol Gastrointest Liver Physiol 280 (2001) G315-G318
257. Ringel Y., and Drossman D.A. Psychosocial aspects of Crohn's disease. Surg Clin North Am 81 (2001) 231-252 x
258. Million M., Tache Y., and Anton P. Susceptibility of Lewis and Fischer rats to stress-induced worsening of TNB-colitis: protective role of brain CRF. Am J Physiol Gastrintest Liver Physiol 276 (1999) G1027-G1036
259. Qiu B.S., Vallance B.A., Blennerhassett P.A., and Collins S.M. The role of CD4+ lymphocytes in the susceptibility of mice to stress-induced reactivation of experimental colitis. Nat Med 5 (1999) 1178-1182
260. Bennett E.J., Tennant C.C., Piesse C., Badcock C.A., and Kellow J.E. Level of chronic life stress predicts clinical outcome in irritable bowel syndrome. Gut 43 (1998) 256-261