Inflammatory bowel disease and celiac disease: Overlaps in the pathology and genetics, and their potential drug targets

Endocrine, Metabolic and Immune Disorders - Drug Targets

Volumn 9, Issue 2, 2009, Pages 199-218

  Festen, Eleonora A M ^a   Szperl, Agata M ^a   Weersma, Rinse K ^a   Wijmenga, Cisca ^a   Wapenaar, Martin C ^a  

^a UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

Author keywords

Celiac disease; Crohn's disease; Inflammatory bowel disease; Intestinal permeability; Mucosal immunity; Th1 response; Th17 response; Ulcerative colitis

Indexed keywords

ACETYLSALICYLIC ACID; CYTOKINE; GAMMA INTERFERON; GLIADIN; IBUPROFEN; INTERLEUKIN 15; INTERLEUKIN 18; INTERLEUKIN 21; LEUKOCYTE ANTIGEN; MUCIN; POLYPEPTIDE ANTIBIOTIC AGENT; PROBIOTIC AGENT; PROTEIN ZO1; TUMOR NECROSIS FACTOR ALPHA; CASPASE RECRUITMENT DOMAIN PROTEIN 15; INTERLEUKIN 17; NOD2 PROTEIN, HUMAN;

ADAPTIVE IMMUNITY; ANTIGEN PRESENTING CELL; ARTICLE; CELIAC DISEASE; CLINICAL TRIAL; CROHN DISEASE; EFFECTOR CELL; ENTERITIS; GENETIC ASSOCIATION; GENETIC PREDISPOSITION; GLUTEN FREE DIET; HUMAN; INNATE IMMUNITY; INTESTINE EPITHELIUM; INTESTINE FLORA; INTESTINE MUCOSA PERMEABILITY; LAMINA PROPRIA; MICROORGANISM; NONHUMAN; T LYMPHOCYTE; TH1 CELL; TH17 CELL; TH2 CELL; ULCERATIVE COLITIS; GENETICS; IMMUNOLOGY; INTESTINE; METABOLISM; PERMEABILITY; PHYSIOLOGY; REVIEW;

CELIAC DISEASE; HUMANS; IMMUNITY, INNATE; INFLAMMATORY BOWEL DISEASES; INTERLEUKIN-17; INTESTINES; NOD2 SIGNALING ADAPTOR PROTEIN; PERMEABILITY; TH1 CELLS; TH2 CELLS;

EID: 67650321838     PISSN: 18715303     EISSN: None     Source Type: Journal    
DOI: 10.2174/187153009788452426     Document Type: Article

References (137)

1. Arrieta, M.C.; Bistritz, L. and Meddings, J.B. (2006) Alterations in intestinal permeability. Gut, 55(10), 1512-1520.
2. DeMeo, M.T.; Mutlu, E.A.; Keshavarzian, A. and Tobin, M.C. (2002) Intestinal permeation and gastrointestinal disease. J. Clin. Gastroenterol., 34(4), 385-396.
3. Shaoul, R.; Okada, Y.; Cutz, E. and Marcon, M.A. (2004) Colonic expression of MUC2, MUC5AC, and TFF1 in inflammatory bowel disease in children. J. Pediatr. Gastroenterol. Nutr., 38(5), 488-493.
4. Corfield, A.P.; Myerscough, N.; Longman, R.; Sylvester, P.; Arul, S. and Pignatelli, M. (2000) Mucins and mucosal protection in the gastrointestinal tract: new prospects for mucins in the pathology of gastrointestinal disease. Gut, 47(4), 589-594.
5. Van Klinken, B.J.; Dekker, J.; van Gool, S.A.; van, M.J.; Buller, H.A. and Einerhand, A.W. (1998) MUC5B is the prominent mucin in human gallbladder and is also expressed in a subset of colonic goblet cells. Am. J. Physiol, 274(5 Pt 1), G871-G878.
6. Dohrman, A.; Miyata, S.; Gallup, M.; Li, J.D.; Chapelin, C.; Coste, A.; Escudier, E.; Nadel, J. and Basbaum, C. (1998) Mucin gene (MUC 2 and MUC 5AC) upregulation by Gram-positive and Gram-negative bacteria. Biochim. Biophys. Acta, 1406(3), 251-259.
7. Cunliffe, R.N.; Rose, F.R.; Keyte, J.; Abberley, L.; Chan, W.C. and Mahida, Y.R. (2001) Human defensin 5 is stored in precursor form in normal Paneth cells and is expressed by some villous epithelial cells and by metaplastic Paneth cells in the colon in inflammatory bowel disease. Gut, 48(2), 176-185.
8. Ouellette, A.J. (1999) IV. Paneth cell antimicrobial peptides and the biology of the mucosal barrier. Am. J. Physiol, 277(2 Pt 1), G257-G261.
9. Schneider, J.J.; Unholzer, A.; Schaller, M.; Schafer-Korting, M. and Korting, H.C. (2005) Human defensins. J. Mol. Med., 83(8), 587-595.
10. Selsted, M.E. and Ouellette, A.J. (2005) Mammalian defensins in the antimicrobial immune response. Nat. Immunol., 6(6), 551-557.
11. Brogden, K.A. (2005) Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol., 3(3), 238-250.
12. Vora, P.; Youdim, A.; Thomas, L.S.; Fukata, M.; Tesfay, S.Y.; Lukasek, K.; Michelsen, K.S.; Wada, A.; Hirayama, T.; Arditi, M. and Abreu, M.T. (2004) Beta-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells. J. Immunol., 173(9), 5398-5405.
13. Ogushi, K.; Wada, A.; Niidome, T.; Mori, N.; Oishi, K.; Nagatake, T.; Takahashi, A.; Asakura, H.; Makino, S.; Hojo, H.; Nakahara, Y.; Ohsaki, M.; Hatakeyama, T.; Aoyagi, H.; Kurazono, H.; Moss, J. and Hirayama, T. (2001) Salmonella enteritidis FliC (flagella filament protein) induces human beta-defensin-2 mRNA production by Caco-2 cells. J. Biol. Chem., 276(32), 30521-30526.
14. Wehkamp, J.; Schmid, M. and Stange, E.F. (2007) Defensins and other antimicrobial peptides in inflammatory bowel disease. Curr. Opin. Gastroenterol., 23(4), 370-378.
15. Moehle, C.; Ackermann, N.; Langmann, T.; Aslanidis, C.; Kel, A.; Kel-Margoulis, O.; Schmitz-Madry, A.; Zahn, A.; Stremmel, W. and Schmitz, G. (2006) Aberrant intestinal expression and allelic variants of mucin genes associated with inflammatory bowel disease. J. Mol. Med., 84(12), 1055-1066.
16. Baumgart, D.C. and Dignass, A.U. (2002) Intestinal barrier function. Curr. Opin. Clin. Nutr. Metab. Care, 5(6), 685-694.
17. Nusrat, A.; Turner, J.R. and Madara, J.L. (2000) Molecular physiology and pathophysiology of tight junctions. IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells. Am. J. Physiol. Gastrointest. Liver Physiol, 279(5), G851-G857.
18. Mitic, L.L.; Van Itallie, C.M. and Anderson, J.M. (2000) 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(2), G250-G254.
19. Fina, D.; Sarra, M.; Caruso, R.; Del Vecchio, B.G.; Pallone, F.; Macdonald, T.T. and Monteleone, G. (2007) Interleukin-21 contributes to the mucosal T helper cell type 1 response in celiac disease. Gut, 57(7), 887-892.
20. Macdonald, T.T. and Monteleone, G. (2005) Immunity, inflammation, and allergy in the gut. Science, 307(5717), 1920-1925.
21. Reims, A.; Strandvik, B. and Sjovall, H. (2006) Epithelial electrical resistance as a measure of permeability changes in pediatric duodenal biopsies. J. Pediatr. Gastroenterol. Nutr., 43(5), 619-623.
22. Baumgart, D.C. and Sandborn, W.J. (2007) Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet, 369(9573), 1641-1657.
23. Lakatos, P.L. (2006) Recent trends in the epidemiology of inflammatory bowel diseases: up or down? World J. Gastroenterol., 12(38), 6102-6108.
24. Van der, S.M.; De Koning, B.A.; De Bruijn, A.C.; Velcich, A.; Meijerink, J.P.; Van Goudoever, J.B.; Buller, H.A.; Dekker, J.; Van, S., I; Renes, I.B. and Einerhand, A.W. (2006) Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology, 131(1), 117-129.
25. McAuley, J.L.; Linden, S.K.; Png, C.W.; King, R.M.; Pennington, H.L.; Gendler, S.J.; Florin, T.H.; Hill, G.R.; Korolik, V. and McGuckin, M.A. (2007) MUC1 cell surface mucin is a critical element of the mucosal barrier to infection. J. Clin. Invest, 117(8), 2313-2324.
26. Buisine, M.P.; Desreumaux, P.; Leteurtre, E.; Copin, M.C.; Colombel, J.F.; Porchet, N. and Aubert, J.P. (2001) Mucin gene expression in intestinal epithelial cells in Crohn's disease. Gut, 49(4), 544-551.
27. Harris, G.; KuoLee, R. and Chen, W. (2006) Role of Toll-like receptors in health and diseases of gastrointestinal tract. World J. Gastroenterol., 12(14), 2149-2160.
28. Baumgart, D.C. and Carding, S.R. (2007) Inflammatory bowel disease: cause and immunobiology. Lancet, 369(9573), 1627-1640.
29. Carneiro, L.A.; Travassos, L.H. and Girardin, S.E. (2007) Nod-like receptors in innate immunity and inflammatory diseases. Ann. Med., 39(8), 581-593.
30. Marks, D.J. and Segal, A.W. (2008) Innate immunity in inflammatory bowel disease: a disease hypothesis. J. Pathol., 214(2), 260-266.
31. Strober, W.; Murray, P.J.; Kitani, A. and Watanabe, T. (2006) Signalling pathways and molecular interactions of NOD1 and NOD2. Nat. Rev. Immunol., 6(1), 9-20.
32. Fukata, M.; Michelsen, K.S.; Eri, R.; Thomas, L.S.; Hu, B.; Lukasek, K.; Nast, C.C.; Lechago, J.; Xu, R.; Naiki, Y.; Soliman, A.; Arditi, M. and Abreu, M.T. (2005) Toll-like receptor-4 is required for intestinal response to epithelial injury and limiting bacterial translocation in a murine model of acute colitis. Am. J. Physiol. Gastrointest. Liver Physiol., 288(5), G1055-G1065.
33. Cario, E. and Podolsky, D.K. (2000) Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect. Immun., 68(12), 7010-7017.
34. Wehkamp, J.; Salzman, N.H.; Porter, E.; Nuding, S.; Weichenthal, M.; Petras, R.E.; Shen, B.; Schaeffeler, E.; Schwab, M.; Linzmeier, R.; Feathers, R.W.; Chu, H.; Lima, H., Jr.; Fellermann, K.; Ganz, T.; Stange, E.F. and Bevins, C.L. (2005) Reduced Paneth cell alpha-defensins in ileal Crohn's disease. Proc. Natl. Acad. Sci. USA, 102(50), 18129-18134.
35. Wehkamp, J.; Harder, J.; Weichenthal, M.; Mueller, O.; Herrlinger, K.R.; Fellermann, K.; Schroeder, J.M. and Stange, E.F. (2003) Inducible and constitutive beta-defensins are differentially expressed in Crohn's disease and ulcerative colitis. Inflamm. Bowel. Dis., 9(4), 215-223.
36. Shi, J. (2007) Defensins and Paneth cells in inflammatory bowel disease. Inflamm. Bowel. Dis., 13(10), 1284-1292.
37. Conte, M.P.; Schippa, S.; Zamboni, I.; Penta, M.; Chiarini, F.; Seganti, L.; Osborn, J.; Falconieri, P.; Borrelli, O. and Cucchiara, S. (2006) Gut-associated bacterial microbiota in paediatric patients with inflammatory bowel disease. Gut, 55(12), 1760-1767.
38. Sasaki, M.; Sitaraman, S.V.; Babbin, B.A.; Gerner-Smidt, P.; Ribot, E.M.; Garrett, N.; Alpern, J.A.; Akyildiz, A.; Theiss, A.L.; Nusrat, A. and Klapproth, J.M. (2007) Invasive Escherichia coli are a feature of Crohn's disease. Lab Invest, 87(10), 1042-1054.
39. Heller, F.; Florian, P.; Bojarski, C.; Richter, J.; Christ, M.; Hillenbrand, B.; Mankertz, J.; Gitter, A.H.; Burgel, N.; Fromm, M.; Zeitz, M.; Fuss, I.; Strober, W. and Schulzke, J.D. (2005) Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology, 129(2), 550-564.
40. Levenstein, S.; Prantera, C.; Varvo, V.; Scribano, M.L.; Andreoli, A.; Luzi, C.; Arca, M.; Berto, E.; Milite, G. and Marcheggiano, A. (2000) Stress and exacerbation in ulcerative colitis: a prospective study of patients enrolled in remission. Am. J. Gastroenterol., 95(5), 1213-1220.
41. Blair, S.A.; Kane, S.V.; Clayburgh, D.R. and Turner, J.R. (2006) Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease. Lab Invest., 86(2), 191-201.
42. Harrington, L.E.; Hatton, R.D.; Mangan, P.R.; Turner, H.; Murphy, T.L.; Murphy, K.M. and Weaver, C.T. (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat. Immunol., 6(11), 1123-1132.
43. Brown, S.J. and Mayer, L. (2007) The immune response in inflammatory bowel disease. Am. J. Gastroenterol., 102(9), 2058-2069.
44. Zhernakova, A.; Festen, E.M.; Franke, L.; Trynka, G.; van Diemen, C.C.; Monsuur, A.J.; Bevova, M.; Nijmeijer, R.M.; van't, S.R.; Heijmans, R.; Boezen, H.M.; van Heel, D.A.; van Bodegraven, A.A.; Stokkers, P.C.; Wijmenga, C.; Crusius, J.B. and Weersma, R.K. (2008) Genetic analysis of innate immunity in Crohn's disease and ulcerative colitis identifies two susceptibility loci harboring CARD9 and IL18RAP. Am. J. Hum. Genet., 82(5), 1202-1210.
45. McGovern, D. and Powrie, F. (2007) The IL23 axis plays a key role in the pathogenesis of IBD. Gut, 56(10), 1333-1336.
46. Yamada, T.; Sartor, R.B.; Marshall, S.; Specian, R.D. and Grisham, M.B. (1993) Mucosal injury and inflammation in a model of chronic granulomatous colitis in rats. Gastroenterology, 104(3), 759-771.
47. Katz, K.D.; Hollander, D.; Vadheim, C.M.; McElree, C.; Delahunty, T.; Dadufalza, V.D.; Krugliak, P. and Rotter, J.I. (1989) Intestinal permeability in patients with Crohn's disease and their healthy relatives. Gastroenterology, 97(4), 927-931.
48. May, G.R.; Sutherland, L.R. and Meddings, J.B. (1993) Is small intestinal permeability really increased in relatives of patients with Crohn's disease? Gastroenterology, 104(6), 1627-1632.
49. Meddings, J.B.; Sutherland, L.R. and May, G.R. (1994) Intestinal permeability in patients with Crohn's disease. Gut, 35(11), 1675-1676.
50. Munkholm, P.; Langholz, E.; Hollander, D.; Thornberg, K.; Orholm, M.; Katz, K.D. and Binder, V. (1994) Intestinal permeability in patients with Crohn's disease and ulcerative colitis and their first degree relatives. Gut, 35(1), 68-72.
51. Peeters, M.; Ghoos, Y.; Maes, B.; Hiele, M.; Geboes, K.; Vantrappen, G. and Rutgeerts, P. (1994) Increased permeability of macroscopically normal small bowel in Crohn's disease. Dig. Dis. Sci., 39(10), 2170-2176.
52. Teahon, K.; Smethurst, P.; Levi, A.J.; Menzies, I.S. and Bjarnason, I. (1992) Intestinal permeability in patients with Crohn's disease and their first degree relatives. Gut, 33(3), 320-323.
53. Soderholm, J.D.; Olaison, G.; Peterson, K.H.; Franzen, L.E.; Lindmark, T.; Wiren, M.; Tagesson, C. and Sjodahl, R. (2002) Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of Crohn's disease. Gut, 50(3), 307-313.
54. Hilsden, R.J.; Meddings, J.B. and Sutherland, L.R. (1996) Intestinal permeability changes in response to acetylsalicylic acid in relatives of patients with Crohn's disease. Gastroenterology, 110(5), 1395-1403.
55. Zamora, S.A.; Hilsden, R.J.; Meddings, J.B.; Butzner, J.D.; Scott, R.B.; Sutherland, L.R. (1999) Intestinal permeability before and after ibuprofen in families of children with Crohn's disease. Can. J. Gastroenterol., 13(1), 31-36.
56. Gitter, A.H.; Wullstein, F.; Fromm, M. and Schulzke, J.D. (2001) Epithelial barrier defects in ulcerative colitis: characterization and quantification by electrophysiological imaging. Gastroenterology, 121(6), 1320-1328.
57. Zeissig, S.; Burgel, N.; Gunzel, D.; Richter, J.; Mankertz, J.; Wahnschaffe, U.; Kroesen, A.J.; Zeitz, M.; Fromm, M. and Schulzke, J.D. (2007) 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(1), 61-72.
58. Bojarski, C.; Gitter, A.H.; Bendfeldt, K.; Mankertz, J.; Schmitz, H.; Wagner, S.; Fromm, M. and Schulzke, J.D. (2001) Permeability of human HT-29/B6 colonic epithelium as a function of apoptosis. J. Physiol, 535(Pt 2), 541-552.
59. Rioux, J.D.; Daly, M.J.; Silverberg, M.S.; Lindblad, K.; Steinhart, H.; Cohen, Z.; Delmonte, T.; Kocher, K.; Miller, K.; Guschwan, S.; Kulbokas, E.J.; O'Leary, S.; Winchester, E.; Dewar, K.; Green, T.; Stone, V.; Chow, C.; Cohen, A.; Langelier, D.; Lapointe, G.; Gaudet, D.; Faith, J.; Branco, N.; Bull, S.B.; McLeod, R.S.; Griffiths, A.M.; Bitton, A.; Greenberg, G.R.; Lander, E.S.; Siminovitch, K.A. and Hudson, T.J. (2001) Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat. Genet., 29(2), 223-228.
60. Waller, S.; Tremelling, M.; Bredin, F.; Godfrey, L.; Howson, J. and Parkes, M. (2006) Evidence for association of OCTN genes and IBD5 with ulcerative colitis. Gut, 55(6), 809-814.
61. Stoll, M.; Corneliussen, B.; Costello, C.M.; Waetzig, G.H.; Mellgard, B.; Koch, W.A.; Rosenstiel, P.; Albrecht, M.; Croucher, P.J.; Seegert, D.; Nikolaus, S.; Hampe, J.; Lengauer, T.; Pierrou, S.; Foelsch, U.R.; Mathew, C.G.; Lagerstrom-Fermer, M. and Schreiber, S. (2004) Genetic variation in DLG5 is associated with inflammatory bowel disease. Nat. Genet., 36(5), 476-480.
62. Van, L.J.; Russell, R.K.; Nimmo, E.R.; Ho, G.T.; Arnott, I.D.; Wilson, D.C. and Satsangi, J. (2007) Genetics of the innate immune response in inflammatory bowel disease. Inflamm. Bowel. Dis., 13(3), 338-355.
63. Wapenaar, M.C.; Monsuur, A.; van, B.A.; Weersma, R.K.; Bevova, M.; Linskens, R.; Howdle, P.; Holmes, G.; Mulder, C.J.; Dijkstra, G.; van Heel, D.A. and Wijmenga, C. (2007) Associations with tight junction genes PARD3 and MAGI2 in Dutch patients point to a common barrier defect for celiac disease and ulcerative colitis. Gut, 57(4), 463-467.
64. van Bodegraven, A.A.; Curley, C.R.; Hunt, K.A.; Monsuur, A.J.; Linskens, R.K.; Onnie, C.M.; Crusius, J.B.; Annese, V.; Latiano, A.; Silverberg, M.S.; Bitton, A.; Fisher, S.A.; Steinhart, A.H.; Forbes, A.; Sanderson, J.; Prescott, N.J.; Strachan, D.P.; Playford, R.J.; Mathew, C.G.; Wijmenga, C.; Daly, M.J.; Rioux, J.D. and van Heel, D.A. (2006) Genetic variation in myosin IXB is associated with ulcerative colitis. Gastroenterology, 131(6), 1768-1774.
65. Marsh, M.N. (1992) Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity ('celiac sprue'). Gastroenterology, 102(1), 330-354.
66. Green, P.H. and Cellier, C. (2007) Celiac disease. N. Engl. J. Med., 357(17), 1731-1743.
67. Greco, L.; Romino, R.; Coto, I.; Di, C.N.; Percopo, S.; Maglio, M.; Paparo, F.; Gasperi, V.; Limongelli, M.G.; Cotichini, R.; D'Agate, C.; Tinto, N.; Sacchetti, L.; Tosi, R. and Stazi, M.A. (2002) The first large population based twin study of coeliac disease. Gut, 50(5), 624-628.
68. Holtmeier, W. and Caspary, W.F. (2006) Celiac disease. Orphanet. J. Rare. Dis., 1, 3.
69. Wolters, V.M. and Wijmenga, C. (2008) Genetic background of celiac disease and its clinical implications. Am. J. Gastroenterol., 103(1), 190-195.
70. Cobden, I.; Dickinson, R.J.; Rothwell, J. and Axon, A.T. (1978) Intestinal permeability assessed by excretion ratios of two molecules: results in coeliac disease. Br. Med. J., 2(6144), 1060.
71. Menzies, I.S.; Laker, M.F.; Pounder, R.; Bull, J.; Heyer, S.; Wheeler, P.G. and Creamer, B. (1979) Abnormal intestinal permeability to sugars in villous atrophy. Lancet, 2(8152), 1107-1109.
72. Schulzke, J.D.; Bentzel, C.J.; Schulzke, I.; Riecken, E.O. and Fromm, M. (1998) Epithelial tight junction structure in the jejunum of children with acute and treated celiac sprue. Pediatr. Res., 43(4 Pt 1), 435-441.
73. Vogelsang, H.; Schwarzenhofer, M. and Oberhuber, G. (1998) Changes in gastrointestinal permeability in celiac disease. Dig. Dis., 16(6), 333-336.
74. Greco, L.; D'Adamo, G.; Truscelli, A.; Parrilli, G.; Mayer, M. and Budillon, G. (1991) Intestinal permeability after single dose gluten challenge in coeliac disease. Arch. Dis. Child, 66(7), 870-872.
75. van Elburg, R.M.; Uil, J.J.; Mulder, C.J. and Heymans, H.S. (1993) Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease. Gut, 34(3), 354-357.
76. Smecuol, E.; Bai, J.C.; Vazquez, H.; Kogan, Z.; Cabanne, A.; Niveloni, S.; Pedreira, S.; Boerr, L.; Maurino, E. and Meddings, J.B. (1997) Gastrointestinal permeability in celiac disease. Gastroenterology, 112(4), 1129-1136.
77. Ukabam, S.O. and Cooper, B.T. (1985) Small intestinal permeability as an indicator of jejunal mucosal recovery in patients with celiac sprue on a gluten-free diet. J. Clin. Gastroenterol., 7(3), 232-236.
78. Duerksen, D.R.; Wilhelm-Boyles, C. and Parry, D.M. (2005) Intestinal permeability in long-term follow-up of patients with celiac disease on a gluten-free diet. Dig. Dis. Sci., 50(4), 785-790.
79. Hall, E.J. and Batt, R.M. (1991) Abnormal permeability precedes the development of a gluten sensitive enteropathy in Irish setter dogs. Gut, 32(7), 749-753.
80. Hall, E.J. and Batt, R.M. (1991) Abnormal intestinal permeability could play a role in the development of gluten-sensitive enteropathy in Irish setter dogs. J. Nutr., 121(11 Suppl), S150-S151.
81. Bethune, M.T.; Borda, J.T.; Ribka, E.; Liu, M.X.; Phillippi-Falkenstein, K.; Jandacek, R.J.; Doxiadis, G.G.; Gray, G.M.; Khosla, C. and Sestak, K. (2008) A non-human primate model for gluten sensitivity. PLoS. ONE., 3(2), e1614.
82. Bethune, M.T.; Ribka, E.; Khosla, C. and Sestak, K. (2008) Transepithelial transport and enzymatic detoxification of gluten in gluten-sensitive rhesus macaques. PLoS. ONE., 3(3), e1857.
83. Dieterich, W.; Esslinger, B. and Schuppan, D. (2003) Pathomechanisms in celiac disease. Int. Arch. Allergy Immunol., 132(2), 98-108.
84. Sollid, L.M. (2002) Coeliac disease: dissecting a complex inflammatory disorder. Nat. Rev. Immunol., 2(9), 647-655.
85. Kagnoff, M.F. (2007) Celiac disease: pathogenesis of a model immunogenetic disease. J. Clin. Invest, 117(1), 41-49.
86. Szebeni, B.; Veres, G.; Dezsofi, A.; Rusai, K.; Vannay, A.; Bokodi, G.; Vasarhelyi, B.; Korponay-Szabo, I.R.; Tulassay, T. and Arato, A. (2007) Increased mucosal expression of Toll-like receptor (TLR)2 and TLR4 in coeliac disease. J. Pediatr. Gastroenterol. Nutr., 45(2), 187-193.
87. Maiuri, L.; Ciacci, C.; Auricchio, S.; Brown, V.; Quaratino, S. and Londei, M. (2000) Interleukin 15 mediates epithelial changes in celiac disease. Gastroenterology, 119(4), 996-1006.
88. Hue, S.; Mention, J.J.; Monteiro, R.C.; Zhang, S.; Cellier, C.; Schmitz, J.; Verkarre, V.; Fodil, N.; Bahram, S.; Cerf-Bensussan, N. and Caillat-Zucman, S. (2004) A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease. Immunity, 21(3), 367-377.
89. Wapenaar, M.C.; van Belzen, M.J.; Fransen, J.H.; Sarasqueta, A.F.; Houwen, R.H.; Meijer, J.W.; Mulder, C.J. and Wijmenga, C. (2004) The interferon gamma gene in celiac disease: augmented expression correlates with tissue damage but no evidence for genetic susceptibility. J. Autoimmun., 23(2), 183-190.
90. Li, Q.; Zhang, Q.; Wang, M.; Zhao, S.; Ma, J.; Luo, N.; Li, N.; Li, Y.; Xu, G. and Li, J. (2008) Interferon-gamma and tumor necrosis factor-alpha disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction. Clin. Immunol., 126(1), 67-80.
91. Wisner, D.M.; Harris, L.R., III; Green, C.L. and Poritz, L.S. (2008) Opposing regulation of the tight junction protein claudin-2 by interferon-gamma and interleukin-4. J. Surg. Res., 144(1), 1-7.
92. Clemente, M.G.; De, V.S.; Kang, J.S.; Macatagney, R.; Musu, M.P.; Di Pierro, M.R.; Drago, S.; Congia, M. and Fasano, A. (2003) Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut, 52(2), 218-223.
93. Montalto, M.; Cuoco, L.; Ricci, R.; Maggiano, N.; Vecchio, F.M. and Gasbarrini, G. (2002) Immunohistochemical analysis of ZO-1 in the duodenal mucosa of patients with untreated and treated celiac disease. Digestion, 65(4), 227-233.
94. Pizzuti, D.; Bortolami, M.; Mazzon, E.; Buda, A.; Guariso, G.; D'Odorico, A.; Chiarelli, S.; D'Inca, R.; De Lazzari, F. and Martines, D. (2004) Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten-free diet. Dig. Liver Dis., 36(5), 337-341.
95. Sander, G.R.; Cummins, A.G.; Henshall, T. and Powell, B.C. (2005) Rapid disruption of intestinal barrier function by gliadin involves altered expression of apical junctional proteins. FEBS Lett., 579(21), 4851-4855.
96. Arthur, J.M. (2000) The MDCK cell line is made up of populations of cells with diverse resistive and transport properties. Tissue Cell, 32(5), 446-450.
97. Lammers, K.M.; Lu, R.; Brownley, J.; Lu, B.; Gerard, C.; Thomas, K.; Rallabhandi, P.; Shea-Donohue, T.; Tamiz, A.; Alkan, S.; Netzel-Arnett, S.; Antalis, T.; Vogel, S.N. and Fasano, A. (2008) Gliadin Induces an Increase in Intestinal Permeability and Zonulin Release by Binding to the Chemokine Receptor CXCR3. Gastroenterology, 135(1):194-204.e3.
98. Thomas, K.E.; Sapone, A.; Fasano, A. and Vogel, S.N. (2006) Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in Celiac disease. J. Immunol., 176(4), 2512-2521.
99. Drago, S.; El, A.R.; Di, P.M.; Grazia, C.M.; Tripathi, A.; Sapone, A.; Thakar, M.; Iacono, G.; Carroccio, A.; D'Agate, C.; Not, T.; Zampini, L.; Catassi, C. and Fasano, A. (2006) Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand. J. Gastroenterol., 41(4), 408-419.
100. Smecuol, E.; Sugai, E.; Niveloni, S.; Vazquez, H.; Pedreira, S.; Mazure, R.; Moreno, M.L.; Label, M.; Maurino, E.; Fasano, A.; Meddings, J. and Bai, J.C. (2005) Permeability, zonulin production, and enteropathy in dermatitis herpetiformis. Clin. Gastroenterol. Hepatol., 3(4), 335-341.
101. Forsberg, G.; Fahlgren, A.; Horstedt, P.; Hammarstrom, S.; Hernell, O. and Hammarstrom, M.L. (2004) Presence of bacteria and innate immunity of intestinal epithelium in childhood celiac disease. Am. J. Gastroenterol., 99(5), 894-904.
102. Tjellstrom, B.; Stenhammar, L.; Hogberg, L.; Falth-Magnusson, K.; Magnusson, K.E.; Midtvedt, T.; Sundqvist, T. and Norin, E. (2005) Gut microflora associated characteristics in children with celiac disease. Am. J. Gastroenterol., 100(12), 2784-2788.
103. Dennehy, P.H. (2000) Transmission of rotavirus and other enteric pathogens in the home. Pediatr. Infect. Dis. J., 19(10 Suppl), S103-S105.
104. Zanoni, G.; Navone, R.; Lunardi, C.; Tridente, G.; Bason, C.; Sivori, S.; Beri, R.; Dolcino, M.; Valletta, E.; Corrocher, R. and Puccetti, A. (2006) In celiac disease, a subset of autoantibodies against transglutaminase binds toll-like receptor 4 and induces activation of monocytes. PLoS. Med., 3(9), e358.
105. Obert, G.; Peiffer, I. and Servin, A.L. (2000) Rotavirus-induced structural and functional alterations in tight junctions of polarized intestinal Caco-2 cell monolayers. J. Virol., 74(10), 4645-4651.
106. Beau, I.; Cotte-Laffitte, J.; Amsellem, R. and Servin, A.L. (2007) A protein kinase A-dependent mechanism by which rotavirus affects the distribution and mRNA level of the functional tight junction-associated protein, occludin, in human differentiated intestinal Caco-2 cells. J. Virol., 81(16), 8579-8586.
107. Yang, A.; Chen, Y.; Scherl, E.; Neugut, A.I.; Bhagat, G. and Green, P.H. (2005) Inflammatory bowel disease in patients with celiac disease. Inflamm. Bowel. Dis., 11(6), 528-532.
108. Leeds, J.S.; Horoldt, B.S.; Sidhu, R.; Hopper, A.D.; Robinson, K.; Toulson, B.; Dixon, L.; Lobo, A.J.; McAlindon, M.E.; Hurlstone, D.P. and Sanders, D.S. (2007) Is there an association between coeliac disease and inflammatory bowel diseases? A study of relative prevalence in comparison with population controls. Scand. J. Gastroenterol., 42(10), 1214-1220.
109. Cottone, M.; Marrone, C.; Casa, A.; Oliva, L.; Orlando, A.; Calabrese, E.; Martorana, G. and Pagliaro, L. (2003) Familial occurrence of inflammatory bowel disease in celiac disease. Inflamm. Bowel. Dis., 9(5), 321-323.
110. Masachs, M.; Casellas, F. and Malagelada, J.R. (2007) Inflammatory bowel disease in celiac patients. Rev. Esp. Enferm. Dig., 99(8), 446-450.
111. Schuppan, D. and Hahn, E.G. (2002) Biomedicine. Gluten and the gut-lessons for immune regulation. Science, 297(5590), 2218-2220.
112. Rioux, K.P. and Fedorak, R.N. (2006) Probiotics in the treatment of inflammatory bowel disease. J. Clin. Gastroenterol., 40(3), 260-263.
113. Marinaro, M.; Fasano, A. and De Magistris, M.T. (2003) Zonula occludens toxin acts as an adjuvant through different mucosal routes and induces protective immune responses. Infect. Immun., 71(4), 1897-1902.
114. Dideberg, V.; Theatre, E.; Farnir, F.; Vermeire, S.; Rutgeerts, P.; Vos, M.D.; Belaiche, J.; Franchimont, D.; Gossum, A.V.; Louis, E. and Bours, V. (2006) The TNF/ADAM 17 system: implication of an ADAM 17 haplotype in the clinical response to infliximab in Crohn's disease. Pharmacogenet. Genomics, 16(10), 727-734.
115. Skak, K.; Kragh, M.; Hausman, D.; Smyth, M.J. and Sivakumar, P.V. (2008) Interleukin 21: combination strategies for cancer therapy. Nat. Rev. Drug Discov., 7(3), 231-240.
116. Hampe, J.; Franke, A.; Rosenstiel, P.; Till, A.; Teuber, M.; Huse, K.; Albrecht, M.; Mayr, G.; De, L., V; Briggs, J.; Gunther, S.; Prescott, N.J.; Onnie, C.M.; Hasler, R.; Sipos, B.; Folsch, U.R.; Lengauer, T.; Platzer, M.; Mathew, C.G.; Krawczak, M. and Schreiber, S. (2007) A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat. Genet., 39(2), 207-211.
117. Satsangi, J.; Welsh, K.I.; Bunce, M.; Julier, C.; Farrant, J.M.; Bell, J.I. and Jewell, D.P. (1996) Contribution of genes of the major histocompatibility complex to susceptibility and disease phenotype in inflammatory bowel disease. Lancet, 347(9010), 1212-1217.
118. Satsangi, J.; Parkes, M.; Louis, E.; Hashimoto, L.; Kato, N.; Welsh, K.; Terwilliger, J.D.; Lathrop, G.M.; Bell, J.I. and Jewell, D.P. (1996) Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12. Nat. Genet., 14(2), 199-202.
119. Silverberg, M.S.; Duerr, R.H.; Brant, S.R.; Bromfield, G.; Datta, L.W.; Jani, N.; Kane, S.V.; Rotter, J.I.; Philip, S.L.; Hillary, S.A.; Taylor, K.D.; Yang, H.; Cho, J.H.; Rioux, J.D. and Daly, M.J. (2007) Refined genomic localization and ethnic differences observed for the IBD5 association with Crohn's disease. Eur. J. Hum. Genet., 15(3), 328-335.
120. Peltekova, V.D.; Wintle, R.F.; Rubin, L.A.; Amos, C.I.; Huang, Q.; Gu, X.; Newman, B.; Van, O.M.; Cescon, D.; Greenberg, G.; Griffiths, A.M.; St George-Hyslop, P.H. and Siminovitch, K.A. (2004) Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat. Genet., 36(5), 471-475.
121. Reinhard, C. and Rioux, J.D. (2006) Role of the IBD5 susceptibility locus in the inflammatory bowel diseases. Inflamm. Bowel. Dis., 12(3), 227-238.
122. Duerr, R.H.; Taylor, K.D.; Brant, S.R.; Rioux, J.D.; Silverberg, M.S.; Daly, M.J.; Steinhart, A.H.; Abraham, C.; Regueiro, M.; Griffiths, A.; Dassopoulos, T.; Bitton, A.; Yang, H.; Targan, S.; Datta, L.W.; Kistner, E.O.; Schumm, L.P.; Lee, A.T.; Gregersen, P.K.; Barmada, M.M.; Rotter, J.I.; Nicolae, D.L. and Cho, J.H. (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science, 314(5804), 1461-1463.
123. Tremelling, M.; Cummings, F.; Fisher, S.A.; Mansfield, J.; Gwilliam, R.; Keniry, A.; Nimmo, E.R.; Drummond, H.; Onnie, C.M.; Prescott, N.J.; Sanderson, J.; Bredin, F.; Berzuini, C.; Forbes, A.; Lewis, C.M.; Cardon, L.; Deloukas, P.; Jewell, D.; Mathew, C.G.; Parkes, M. and Satsangi, J. (2007) IL23R variation determines susceptibility but not disease phenotype in inflammatory bowel disease. Gastroenterology, 132(5), 1657-1664.
124. Parkes, M.; Barrett, J.C.; Prescott, N.J.; Tremelling, M.; Anderson, C.A.; Fisher, S.A.; Roberts, R.G.; Nimmo, E.R.; Cummings, F.R.; Soars, D.; Drummond, H.; Lees, C.W.; Khawaja, S.A.; Bagnall, R.; Burke, D.A.; Todhunter, C.E.; Ahmad, T.; Onnie, C.M.; McArdle, W.; Strachan, D.; Bethel, G.; Bryan, C.; Lewis, C.M.; Deloukas, P.; Forbes, A.; Sanderson, J.; Jewell, D.P.; Satsangi, J.; Mansfield, J.C.; Cardon, L. and Mathew, C.G. (2007) Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat. Genet., 39(7), 830-832.
125. Onnie, C.M.; Fisher, S.A.; Pattni, R.; Sanderson, J.; Forbes, A.; Lewis, C.M. and Mathew, C.G. (2006) Associations of allelic variants of the multidrug resistance gene (ABCB1 or MDR1) and inflammatory bowel disease and their effects on disease behavior: a case-control and meta-analysis study. Inflamm. Bowel. Dis., 12(4), 263-271.
126. Ho, G.T.; Soranzo, N.; Nimmo, E.R.; Tenesa, A.; Goldstein, D.B. and Satsangi, J. (2006) ABCB1/MDR1 gene determines susceptibility and phenotype in ulcerative colitis: discrimination of critical variants using a gene-wide haplotype tagging approach. Hum. Mol. Genet., 15(5), 797-805.
127. Hugot, J.P.; Chamaillard, M.; Zouali, H.; Lesage, S.; Cezard, J.P.; Belaiche, J.; Almer, S.; Tysk, C.; O'Morain, C.A.; Gassull, M.; Binder, V.; Finkel, Y.; Cortot, A.; Modigliani, R.; Laurent-Puig, P.; Gower-Rousseau, C.; Macry, J.; Colombel, J.F.; Sahbatou, M. and Thomas, G. (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature, 411(6837), 599-603.
128. Browning, B.L.; Huebner, C.; Petermann, I.; Gearry, R.B.; Barclay, M.L.; Shelling, A.N. and Ferguson, L.R. (2007) Has toll-like receptor 4 been prematurely dismissed as an inflammatory bowel disease gene? Association study combined with meta-analysis shows strong evidence for association. Am. J. Gastroenterol., 102(11), 2504-2512.
129. Libioulle, C.; Louis, E.; Hansoul, S.; Sandor, C.; Farnir, F.; Franchimont, D.; Vermeire, S.; Dewit, O.; de, V.M.; Dixon, A.; Demarche, B.; Gut, I.; Heath, S.; Foglio, M.; Liang, L.; Laukens, D.; Mni, M.; Zelenika, D.; Van, G.A.; Rutgeerts, P.; Belaiche, J.; Lathrop, M. and Georges, M. (2007) Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4. PLoS. Genet., 3(4), e58.
130. Vogelsang, H.; Schwarzenhofer, M.; Steiner, B.; Wyatt, J. and Oberhuber, G. (2001) In vivo and in vitro permeability in coeliac disease. Aliment. Pharmacol. Ther., 15(9), 1417-1425.
131. Vilela, E.G.; de Abreu Ferrari, M.L.; de Gama Torres, H.O.; Martins, F.P.; Goulart, E.M.; Lima, A.S. and da Cunha, A.S. (2007) Intestinal permeability and antigliadin antibody test for monitoring adult patients with celiac disease. Dig. Dis. Sci., 52(5), 1304-1309.
132. Bjarnason, I.; Marsh, M.N.; Price, A.; Levi, A.J. and Peters, T.J. (1985) Intestinal permeability in patients with coeliac disease and dermatitis herpetiformis. Gut, 26(11), 1214-1219.
133. Festen, E.A.M.; Zhernakova, A. and Weersma, R.K. (2008) Association of DLG5 variants with gluten sensitive enteropathy. Gut, 57(7), 1027-1028.
134. Hunt, K.A.; Zhernakova, A.; Turner, G.; Heap, G.A.; Franke, L.; Bruinenberg, M.; Romanos, J.; Dinesen, L.C.; Ryan, A.W.; Panesar, D.; Gwilliam, R.; Takeuchi, F.; McLaren, W.M.; Holmes, G.K.; Howdle, P.D.; Walters, J.R.; Sanders, D.S.; Playford, R.J.; Trynka, G.; Mulder, C.J.; Mearin, M.L.; Verbeek, W.H.; Trimble, V.; Stevens, F.M.; O'morain, C.; Kennedy, N.P.; Kelleher, D.; Pennington, D.J.; Strachan, D.P.; McArdle, W.L.; Mein, C.A.; Wapenaar, M.C.; Deloukas, P.; McGinnis, R.; McManus, R.; Wijmenga, C. and van Heel, D.A. (2008) Newly identified genetic risk variants for celiac disease related to the immune response. Nat. Genet., 40(4), 395-402.
135. Monsuur, A.J.; de Bakker, P.I.; Alizadeh, B.Z.; Zhernakova, A.; Bevova, M.R.; Strengman, E.; Franke, L.; van't, S.R.; van Belzen, M.J.; Lavrijsen, I.C.; Diosdado, B.; Daly, M.J.; Mulder, C.J.; Mearin, M.L.; Meijer, J.W.; Meijer, G.A.; van, O.E.; Wapenaar, M.C.; Koeleman, B.P. and Wijmenga, C. (2005) Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect. Nat. Genet., 37(12), 1341-1344.
136. Lettesjo, H.; Hansson, T.; Bergqvist, A.; Gronlund, J. and Dannaeus, A. (2005) Enhanced interleukin-18 levels in the peripheral blood of
137. Lahat, N.; Shapiro, S.; Karban, A.; Gerstein, R.; Kinarty, A. and Lerner, A. (1999) Cytokine profile in coeliac disease. Scand. J. Immunol., 49(4), 441-446.