Intestinal epithelial barrier dysfunction in disease and possible therapeutical interventions

Current Medicinal Chemistry

Volumn 18, Issue 3, 2011, Pages 398-426

  Catalioto, R M ^a   Maggi, C A ^a   Giuliani, S ^a  

^a Menarini Ricerche SpA   (Italy)

Author keywords

Growth factors; Inflammatory bowel disease; Intestinal epithelial cells; Myosin light chain kinase; NF kB; Probiotics; Protease activated receptor 2; Tight junction

Indexed keywords

ACETALDEHYDE; AG 012; ALCOHOL; ANTIGEN; DA 6034; DIMS 0150; GAMMA INTERFERON; GLIADIN; GROWTH FACTOR; HE 3286; HMPL 004; I KAPPA B; INTERLEUKIN 1; INTERLEUKIN 8; K 12940; K 14585; LARAZOTIDE; MS 444; MS 681; MYOSIN LIGHT CHAIN KINASE; MYOSIN LIGHT CHAIN KINASE INHIBITOR; PROBIOTIC AGENT; REPIFERMIN; TEDUGLUTIDE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VELAFERMIN; VGX 1027; ZP 1846; ZP 1848;

ARTICLE; CELIAC DISEASE; COLITIS; COLLAGENOUS COLITIS; CROHN DISEASE; DIABETES MELLITUS; DIARRHEA; DRUG ABSORPTION; DRUG STRUCTURE; ENDOCYTOSIS; ENTERITIS; ENTEROPATHY; FOOD ALLERGY; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INTESTINE EPITHELIUM; INTESTINE EPITHELIUM CELL; INTESTINE INFECTION; INTESTINE ISCHEMIA; INTESTINE MUCOSA PERMEABILITY; IRRITABLE COLON; NONHUMAN; PERMEABILITY BARRIER; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; ULCERATIVE COLITIS;

EID: 79251519296     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986711794839179     Document Type: Article

References (234)

1. Anderson, J.M.; Van Itallie, C.M. Physiology and function of the tight junction. Cold Spring Harb. Perspect. Biol., 2009, 1, a002584.
2. Groschwitz, K.R.; Hogan, S.P. Intestinal barrier function: Molecular regulation and disease pathogenesis. J. Allergy Clin. Immunol., 2009, 124(1), 3-20.
3. Tsukita, S.; Yamazaki, Y.; Katsuno, T.; Tamura, A.; Tsukita, S. Tight junction-based epithelial microenvironment and cell proliferation. Oncogene, 2008, 27(55), 6930-6938.
4. Fasano, A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation living life on the edge of the wall. Am. J. Pathol., 2008, 173(5), 1243-1252.
5. Förster, C. Tight junctions and the modulation of barrier function in disease. Histochem. Cell. Biol., 2008, 130(1), 55-70.
6. González-Mariscal, L.; Tapia, R.; Chamorro, D. Crosstalk of tight junction components with signaling pathways. Biochim. Biophys. Acta, 2008, 1778(3), 729-756.
7. Shen, L.; Black, E.D.; Witkowski, E.D.; Lencer, W.I.; Guerriero, V.; Schneeberger, E.E.; Turner, J.R. Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure. J. Cell. Sci., 2006, 119(10), 2095-2106.
8. Keita, A.V.; Söderholm, J.D. The intestinal barrier and its regulation by neuroimmune factors. Neurogastroenterol. Motil., 2010, 22(7), 718-733.
9. Guttman, J.A.; Finlay, B.B. Tight junctions as targets of infectious agents. Biochim. Biophys. Acta, 2009, 1788(4), 832-841.
10. Wang, W.; Uzzau, S.; Goldblum, S.E.; Fasano, A. Human zonulin, a potential modulator of intestinal tight junctions. J. Cell. Sci., 2000, 113(24), 4435-4440.
11. Ivanov, A.I.; Nusrat, A.; Parkos, C.A. The epithelium in inflammatory bowel disease: Potential role of endocytosis of junctional proteins in barrier disruption. Novartis Foundation Symp. J., 2004, 263, 115-124.
12. Yu, D.; Turner, J.R. Stimulus-induced reorganization of tight junction structure: The role of membrane traffic. Biochim. Biophys. Acta, 2008, 1778(3), 709-716.
13. Ivanov, A.I.; Parkos, C.A.; Nusrat, A. Cytoskeletal regulation of epithelial barrier function during inflammation. Am. J. Pathol., 2010, 177(2), 512-524.
14. Marchiando, A.M.; Shen, L.; Graham, W.V.; Weber, C.R.; Schwarz, B.T.; Austin, J.R.; Raleigh, D.R.; Guan, Y.; Watson, A.J.; Montrose, M.H.; Turner, J.R. Caveolin-1-dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo. J. Cell. Biol., 2010, 189(1), 111-126.
15. Yu, D.; Marchiando, A.M.; Weber, C.R.; Raleigh, D.R.; Wang, Y.; Shen, L.; Turner, J.R. MLCK-dependent exchange and actin binding region-dependent anchoring of ZO-1 regulate tight junction barrier function. Proc. Natl. Acad. Sci. USA, 2010, 107(18), 8237-8241.
16. Samarin, S.; Nusrat, A. Regulation of epithelial apical junctional complex by Rho family GTPases. Front. Biosci., 2009, 14, 1129-1142.
17. Buzza, M.S.; Netzel-Arnett, S.; Shea-Donohue, T.; Zhao, A.; Lin, C.Y.; List, K.; Szabo, R.; Fasano, A.; Bugge, T.H.; Antalis, T.M. Membrane-anchored serine protease matriptase regulates epithelial barrier formation and permeability in the intestine. Proc. Natl. Acad. Sci. USA, 2010, 107(9), 4200-4205.
18. Marchiando, A.M.; Graham, W.V.; Turner, J.R. Epithelial barriers in homeostasis and disease. Annu. Rev. Pathol., 2010, 5, 119-144.
19. Schmitz, H.; Barmeyer, C.; Fromm, M.; Runkel, N.; Foss, H.D.; Bentzel, C.J.; Riecken, E.O.; Schulzke, J.D. Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis. Gastroenterology, 1999, 116(2), 301-309.
20. Zeissig, S; Bürgel, N.; Günzel, D.; Richter, J.; Mankertz, J.; Wahnschaffe, U.; Kroesen, A.J.; Zeitz, M.; Fromm, M.; Schulzke, J.D. 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, 2007, 56(1), 61-72.
21. D'Inca, R.; Di Leo, V.; Corrao, G.; Martines, D.; D'odorico, A.; Mestriner, C.; Venturi, C.; Longo, G.; Sturniolo, G.C. Intestinal permeability test as a predictor of clinical course in Crohn's disease. Am. J. Gastroenterol., 1999, 94(10), 2956-2960.
22. Irvine, E.J.; Marshall, J.K. Increased intestinal permeability precedes the onset of Crohn's disease in a subject with familial risk. Gastroenterology, 2000, 119(6), 1740-1744.
23. Wild, G.E.; Waschke, K.A.; Bitton, A.; Thomson, A.B. The mechanisms of prednisone inhibition of inflammation in Crohn's disease involve changes in intestinal permeability, mucosal TNFalpha production and nuclear factor kappa B expression. Aliment. Pharmacol. Ther., 2003, 18(3), 309-317.
24. Miele, E.; Pascarella, F.; Quaglietta, L.; Giannetti, E.; Greco, L.; Troncone, R.; Staiano, A. Altered intestinal permeability is predictive of early relapse in children with steroid-responsive ulcerative colitis. Aliment. Pharmacol. Ther., 2007, 25(8), 933-939.
25. Thuijls, G.; Derikx, J.P.; de Haan, J.J.; Grootjans, J.; de Bruïne, A.; Masclee, A.A.; Heineman, E.; Buurman, W.A. Urine-based detection of intestinal tight junction loss. Gastroenterology, 2010, 44(1), e14-e19.
26. Amasheh, S.; Dullat, S.; Fromm, M.; Schulzke, J.D.; Buhr, H.J.; Kroesen, A.J. Inflamed pouch mucosa possesses altered tight junctions indicating recurrence of inflammatory bowel disease. Int. J. Colorectal. Dis., 2009, 24(10), 1149-1156.
27. Gassler, N.; Rohr, C.; Schneider, A.; Kartenbeck, J.; Bach, A.; Obermüller, N.; Otto, H.F.; Autschbach, F. Inflammatory bowel disease is associated with changes of enterocytic junctions. Am. J. Physiol. Gastrointest. Liver Physiol., 2001, 281(1), G216-G228.
28. Kucharzik, T.; Walsh, S.V.; Chen, J.; Parkos, C.A.; Nusrat, A. Neutrophil transmigration in inflammatory bowel disease is associated with differential expression of epithelial intercellular junction proteins. Am. J. Pathol., 2001, 159(6), 2001-2009.
29. Söderholm, J.D; Olaison, G.; Peterson, K.H.; Franzén, L.E.; Lindmark, T.; Wirén, M.; Tagesson, C.; Sjödahl, R. Augmented increase in tight junction permeability by luminal stimuli in the noninflamed ileum of Crohn's disease. Gut, 2002, 50(3), 307-313.
30. Zwiers, A.; Fuss, I.J.; Leijen, S.; Mulder, C.J.; Kraal, G.; Bouma, G. Increased expression of the tight junction molecule claudin-18 A1 in both experimental colitis and ulcerative colitis. Inflamm. Bowel. Dis., 2008, 14(12), 1652-1659.
31. Bürgel, N.; Bojarski, C.; Mankertz, J.; Zeitz, M.; Fromm, M.; Schulzke, J.D. Mechanisms of diarrhea in collagenous colitis. Gastroenterology, 2002, 123(2), 433-443.
32. Prasad, S.; Mingrino, R.; Kaukinen, K.; Hayes, K.L.; Powell, R.M.; MacDonald, T.T.; Collins, J.E. Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells. Lab. Invest., 2005, 85, 1139-1162.
33. Oshima, T.; Miwa, H.; Joh, T. Changes in the expression of claudins in active ulcerative colitis. J. Gastroenterol. Hepatol., 2008, 23(suppl2), S146-S150.
34. Weber, C.R.; Nalle, S.C.; Tretiakova, M.; Rubin, D.T.; Turner, J.R. Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation. Lab. Invest., 2008, 88(10), 1110-1120.
35. 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.; van Heel, D.A. Genetic variation in myosin IXB is associated with ulcerative colitis. Gastroenterology, 2006, 131(6), 1768-1774.
36. Cooney, R.; Cummings, J.R.; Pathan, S.; Beckly, J.; Geremia, A.; Hancock, L.; Guo, C.; Morris, A.; Jewell, D.P. Association between genetic variants in myosin IXB and Crohn's disease. Inflamm. Bowel. Dis., 2009, 15(7), 1014-1021.
37. Wapenaar, M.C.; Monsuur, A.J.; van Bodegraven, A.A.; Weersma, R.K.; Bevova, M.R.; Linskens, R.K.; Howdle, P.; Holmes, G.; Mulder, C.J.; Dijkstra, G.; van Heel, D.A.; Wijmenga, C. Intestinal inflammation. Associations with tight junction genes PARD3 and MAGI2 in Dutch patients point to a common barrier defect for coeliac disease and ulcerative colitis. Gut, 2008, 57, 463-467.
38. McGovern, D.P.B.; Taylor, K.D.; Landers, C.; Derkowski, C.; Dutridge, D.; Dubinsky, M.; Ippoliti, A.; Vasiliauskas, E.; Mei, L.; Mengesha, E.; King, L.; Pressman, S.; Targan, S.R.; Rotter, J.I. MAGI2 genetic variation and inflammatory bowel disease. Inflamm. Bowel. Dis., 2009, 15, 75-83.
39. 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.; Klapproth, J.-M.A. Invasive Escherichia coli are a feature of Crohn's disease. Lab. Invest., 2007, 87(10), 1042-1054.
40. La Ferla, K.; Seegert, D.; Schreiber, S. Activation of NF-kappaB in intestinal epithelial cells by E. coli strains isolated from the colonic mucosa of IBD patients. Int. J. Colorectal. Dis., 2004, 19(4), 334-342.
41. Piche, T.; Barbara, G.; Aubert, P.; Bruley des Varannes, S.; Dainese, R.; Nano, J.L.; Cremon, C.; Stanghellini, V.; De Giorgio, R.; Galmiche, J.P.; Neunlist, M. Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: Involvement of soluble mediators. Gut, 2009, 58(2), 196-201.
42. Gecse, K.; Róka, R.; Ferrier, L.; Leveque, M.; Eutamene, H.; Cartier, C.; Ait-Belgnaoui, A.; Rosztóczy, A.; Izbéki, F.; Fioramonti, J.; Wittmann, T.; Bueno, L. Increased faecal serine protease activity in diarrhoeic IBS patients: A colonic lumenal factor impairing colonic permeability and sensitivity. Gut, 2008, 57(5), 591-599.
43. Dabek, M.; Ferrier, L.; Roka, R.; Gecse, K.; Annahazi, A.; Moreau, J.; Escourrou, J.; Cartier, C.; Chaumaz, G.; Leveque, M.; Ait- Belgnaoui, A.; Wittmann, T.; Theodorou, V.; Bueno, L. Luminal cathepsin G and protease-activated receptor 4: A duet involved in alterations of the colonic epithelial barrier in ulcerative colitis. Am. J. Pathol., 2009, 175(1), 207-214.
44. Fries, W.; Mazzon, E.; Squarzoni, S.; Martin, A.; Martines, D.; Micali, A.; Sturniolo, G.C.; Citi, S.; Longo, G. Experimental colitis increases small intestine permeability in the rat. Lab. Invest., 1999, 79(1), 49-57.
45. Ekström, G.M.; Andersson, S.E. Plasma exudation, hyperaemia, and epithelial permeability in rats with oxazolone-induced colitis: Modulatory effects of budesonide. Scand. J. Gastroenterol., 2000, 35(2), 190-197.
46. Kitajima, S.; Takuma, S.; Morimoto, M. Changes in colonic mucosal permeability in mouse colitis induced with dextran sulfate sodium. Exp. Anim., 1999, 48(3), 137-143.
47. Zuccato, E.; Bertolo, C.; Colombo, L.; Mussini, E. Indomethacininduced enteropathy: Effect of the drug regimen on intestinal permeability in rats. Agents Actions, 1992, Spec No, C18-C21.
48. Madsen, K.L.; Malfair, D.; Gray, D.; Doyle, J.S.; Jewell, L.D.; Fedorak R.N. Interleukin-10 gene-deficient mice develop a primary intestinal permeability defect in response to enteric microflora. Inflamm. Bowel. Dis., 1999, 5(4), 262-270.
49. Laukoetter, M.G.; Nava, P.; Lee, W.Y.; Severson, E.A.; Capaldo, C.T.; Babbin, B.A.; Williams, I.R.; Koval, M.; Peatman, E.; Campbell, J.A.; Dermody, T.S.; Nusrat, A.; Parkos, C.A. JAM-A regulates permeability and inflammation in the intestine in vivo. J. Exp. Med., 2007, 204(13), 3067-3076.
50. Su, L.; Shen, L.; Clayburgh, D.R.; Nalle, S.C.; Sullivan, E.A.; Meddings, J.B.; Abraham, C.; Turner, J.R. Targeted epithelial tight junction dysfunction causes immune activation and contributes to development of experimental colitis. Gastroenterology, 2009, 136(2), 551-563.
51. Resta-Lenert, S.; Smitham, J.; Barrett, K.E. Epithelial dysfunction associated with the development of colitis in conventionally housed mdr1a-/- mice. Am. J. Physiol. Gastrointest. Liver. Physiol., 2005, 289(1), 153-162.
52. Tang, Y.; Clayburgh, D.R.; Mittal, N.; Goretsky, T.; Dirisina, R.; Zhang, Z.; Kron, M.; Ivancic, D.; Katzman, R.B.; Grimm, G.; Lee, G.; Fryer, J.; Nusrat, A.; Turner, J.R.; Barrett, T.A. Epithelial NF{kappa}B enhances transmucosal fluid movement by altering tight junction protein composition after T cell activation. Am. J. Pathol., 2010, 176(1), 158-167.
53. Olson, T.S.; Reuter, B.K.; Scott, K.G.; Morris, M.A.; Wang, X.M.; Hancock, L.N., Burcin, T.L.; Cohn, S.M.; Ernst, P.B.; Cominelli, F.; Meddings, J.B.; Ley, K.; Pizarro, T.T. The primary defect in experimental ileitis originates from a nonhematopoietic source. J. Exp. Med., 2006, 203(3), 541-552.
54. Meddings, J.B.; Jarand, J.; Urbanski, S.J.; Hardin, J.; Gall, D.G. Increased gastrointestinal permeability is an early lesion in the spontaneously diabetic BB rat. Am. J. Physiol., 1999, 276(4 Pt 1), G951-G957.
55. Brun, P.; Castagliuolo, I.; Di Leo, V.; Buda, A.; Pinzani, M.; Palú, G.; Martines, D. Increased intestinal permeability in obese mice: New evidence in the pathogenesis of nonalcoholic steatohepatitis. Am. J. Physiol. Gastrointest. Liver Physiol., 2007, 292(2), G518-G525.
56. Yang, H.; Finaly, R.; Teitelbaum, D.H. Alteration in epithelial permeability and ion transport in a mouse model of total parenteral nutrition. Crit. Care Med., 2003, 31(4), 1118-1125.
57. Gareau, M.G.; Silva, M.A.; Perdue, M.H. Pathophysiological mechanisms of stress-induced intestinal damage. Curr. Mol. Med., 2008, 8(4), 274-281.
58. Reuter, B.K.; Pizarro, T.T. Mechanisms of tight junction dysregulation in the SAMP1/YitFc model of Crohn's disease-like ileitis. Molecular structure and function of the tight junction. Ann. N.Y. Acad. Sci., 2009, 1165, 301-307.
59. Poritz, L.S.; Garver, K.I.; Green, C.; Fitzpatrick, L.; Ruggiero, F.; Koltun, W.A. Loss of the tight junction protein ZO-1 in dextran sulfate sodium induced colitis. J. Surg. Res., 2007, 140(1), 12-19.
60. Vetrano, S.; Rescigno, M.; Cera, M.R.; Correale, C.; Rumio, C.; Doni, A.; Fantini, M.; Sturm, A.; Borroni, E.; Repici, A.; Locati, M.; Malesci, A.; Dejana, E.; Danese, S. Unique role of junctional adhesion molecule-A in maintaining mucosal homeostasis in inflammatory bowel disease. Gastroenterology, 2008, 135(1), 173-184.
61. Colpaert, S.; Liu, Z.; De Greef, B.; Rutgeerts, P.; Ceuppens J.L.; Geboes, K. Effects of anti-tumour necrosis factor, interleukin-10 and antibiotic therapy in the indometacin-induced bowel inflammation rat model. Aliment. Pharmacol. Ther., 2001, 15, 1827-1836.
62. Porras, M.; Martín, M.T.; Yang, P.C.; Jury, J.; Perdue, M.H.; Vergara, P. Correlation between cyclical epithelial barrier dysfunction and bacterial translocation in the relapses of intestinal inflammation. Inflamm. Bowel. Dis., 2006, 12(9), 843-852.
63. Fries, W.; Muja, C.; Crisafulli, C.; Cuzzocrea, S.; Mazzon, E. Dynamics of enterocyte tight junctions: Effect of experimental colitis and two different anti-TNF strategies. Am. J. Physiol. Gastrointest. Liver Physiol., 2008, 294(4), G938-G947.
64. Collett, A.; Higgs, N.B.; Gironella, M.; Zeef, L.A.; Hayes, A.; Salmo, E.; Haboubi, N.; Iovanna, J.L.; Carlson, G.L.; Warhurst, G. Early molecular and functional changes in colonic epithelium that precede increased gut permeability during colitis development in mdr1a(-/-) mice. Inflamm. Bowel. Dis., 2008, 14(5), 620-631.
65. Schuppan, D.; Junker, Y.; Barisani, D. Celiac disease: From pathogenesis to novel therapies. Gastroenterology., 2009, 137(6), 1912-1933.
66. Fasano, A.; Not, T.; Wang, W.; Uzzau, S.; Berti, I.; Tommasini, A.; Goldblum, S.E. Zonulin; a newly discovered modulator of intestinal permeability; and its expression in coeliac disease. Lancet, 2000, 355(9214), 1518-1519.
67. Pizzuti, D.; Bortolami, M.; Mazzon, E.; Buda, A.; Guariso, G.; D'Odorico, A.; Chiarelli, S.; D'Incá, R.; De Lazzari, F.; Martines, D. Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten-free diet. Dig. Liver Dis., 2004, 36(5), 337-341.
68. Ciccocioppo, R.; Finamore, A.; Ara, C.; Di Sabatino, A.; Mengheri, E.; Corazza, G.R. Altered expression, localization, and phosphorylation of epithelial junctional proteins in celiac disease. Am. J. Clin. Pathol., 2006, 125(4), 502-511.
69. Lee, A.S.; Gibson, D.L.; Zhang, Y.; Sham, H.P.; Vallance, B.A.; Dutz, J.P. Gut barrier disruption by an enteric bacterial pathogen accelerates insulitis in NOD mice. Diabetologia, 2010, 53(4),741-748.
70. Cani, P.D.; Possemiers, S.; Van de Wiele, T.; Guiot, Y.; Everard, A.; Rottier, O.; Geurts, L.; Naslain, D.; Neyrinck, A.; Lambert, D.M.; Muccioli, G.G.; Delzenne, N.M. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut, 2009, 58(8), 1091-1103.
71. Bosi, E.; Molteni, L.; Radaelli, M.G.; Folini, L.; Fermo, I.; Bazzigaluppi, E.; Piemonti, L.; Pastore, M.R.; Paroni, R. Increased intestinal permeability precedes clinical onset of type 1 diabetes. Diabetologia, 2006, 49(12), 2824-2827.
72. Sapone, A.; de Magistris, L.; Pietzak, M.; Clemente, M.G.; Tripathi, A.; Cucca, F.; Lampis, R.; Kryszak, D.; Cartení, M.; Generoso, M.; Iafusco, D.; Prisco, F.; Laghi, F.; Riegler, G.; Carratu, R.; Counts, D.; Fasano, A. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes, 2006, 55(5), 1443-1449.
73. Watts, T.; Berti, I.; Sapone, A.; Gerarduzzi, T.; Not, T.; Zielke, R.; Fasano, A. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc. Natl. Acad. Sci. USA, 2005, 102(8), 2916-2921.
74. Ménard, S.; Cerf-Bensussan, N.; Heyman, M. Multiple facets of intestinal permeability and epithelial handling of dietary antigens. Mucosal Immunol., 2010, 3(3), 247-259.
75. Söderholm, J.D.; Streutker, C.; Yang, P.C.; Paterson, C.; Singh, P.K.; McKay, D.M.; Sherman, P.M.; Croitoru, K.; Perdue, M.H. Increased epithelial uptake of protein antigens in the ileum of Crohn's disease mediated by tumour necrosis factor alpha. Gut, 2004, 53(12), 1817-1824.
76. Kersting, S.; Bruewer, M.; Schuermann, G.; Klotz, A.; Utech, M.; Hansmerten, M.; Krieglstein, C.F.; Senninger, N.; Schulzke, J.D.; Naim, H.Y.; Zimmer, K.P. Antigen transport and cytoskeletal characteristics of a distinct enterocyte population in inflammatory bowel diseases. Am. J. Pathol., 2004, 165(2), 425-437.
77. Reinke, Y.; Zimmer, K.P.; Naim, H.Y. Toxic peptides in Frazer's fraction interact with the actin cytoskeleton and affect the targeting and function of intestinal proteins. Exp. Cell. Res., 2009, 315(19), 3442-3452.
78. Hundorfean, G.; Zimmer, K.-P.; Strobel, S.; Gebert, A.; Ludwig, D.; Büning, J. Luminal antigens access late endosomes of intestinal epithelial cells enriched in MHC I and MHC II molecules: In vivo study in Crohn's ileitis. Am. J. Physiol. Gastrointest. Liver Physiol., 2007, 293, G798-G808.
79. Zimmer, K.P.; Fischer, I.; Mothes, T.; Weissen-Plenz, G.; Schmitz, M.; Wieser, H.; Büning, J.; Lerch, M.M.; Ciclitira, P.C.; Weber, P.; Naim, H.Y. Endocytotic segregation of gliadin peptide 31-49 in enterocytes. Gut, 2010, 59(3), 300-310.
80. Matysiak-Budnik, T.; Moura, I.C.; Arcos-Fajardo, M.; Lebreton, C.; Ménard, S.; Candalh, C.; Ben-Khalifa, K.; Dugave, C.; Tamouza, H.; van Niel, G.; Bouhnik, Y.; Lamarque, D.; Chaussade, S.; Malamut, G.; Cellier, C.; Cerf-Bensussan, N.; Monteiro, R.C.; Heyman, M. Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease. J. Exp. Med., 2008, 205(1), 143-154.
81. Heyman, M.; Menard, S. Pathways of gliadin transport in celiac disease. Ann. N. Y. Acad. Sci., 2009, 1165, 274-278.
82. Al-Sadi, R.; Boivin, M.; Ma, T. Mechanism of cytokine modulation of epithelial tight junction barrier. Front. Biosci., 2009, 14, 2765-2778.
83. Capaldo, C.T.; Nusrat, A. Cytokine regulation of tight junctions. Biochim. Biophys. Acta, 2009, 1788(4), 864-871.
84. Youakim, A.; Ahdieh, M. Interferon-γ decreases barrier function in T84 cells by reducing ZO-1 levels and disrupting apical actin. Am. J. Physiol. Gastrointest. Liver Physiol., 1999, 276(39), G1279-G1288.
85. Watson, C.J.; Hoare, C.J.; Garrod, D.R.; Carlson, G.L.; Warhurst, G. Interferon-γ selectively increases epithelial permeability to large molecules by activating different populations of paracellular pores. J. Cell. Sci., 2005, 118(22), 5221-5230.
86. Bruewer, M.; Luegering, A.; Kucharzik, T.; Parkos, C.A.; Madara, J.L.; Hopkins, A.M.; Nusrat, A. Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms. J. Immunol., 2003, 171(11), 6164-6172.
87. Ma, T.Y.; Iwamoto, G.K.; Hoa, N.T.; Akotia, V.; Pedram, A.; Boivin, M.A.; Said, H.M. TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation. Am. J. Physiol. Gastrointest. Liver Physiol., 2004, 286(3), G367-G376.
88. Mankertz, J.; Amasheh, M.; Krug, S.M.; Fromm, A.; Amasheh, S.; Hillenbrand, B.; Tavalali, S.; Fromm, M.; Schulzke, J.D. TNFα upregulates claudin-2 expression in epithelial HT-29/B6 cells via phosphatidylinositol-3- kinase signaling. Cell. Tissue Res., 2009, 336(1), 67-77.
89. Li, Q.; Zhang, Q.; Wang, M.; Zhao, S.; Ma, J.; Luo, N.; Li, N.; Li, Y.; Xu, G.; Li, J. Interferon-gamma and tumor necrosis factoralpha disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction. Clin. Immunol., 2008, 126(1), 67-80.
90. Wang, F.; Graham, W.V.; Wang, Y.; Witkowski, E.D.; Schwarz, B.T.; Turner, J.R. Interferon-gamma and tumor necrosis factoralpha synergize to induce intestinal epithelial barrier dysfunction by up-regulating myosin light chain kinase expression. Am. J. Pathol., 2005, 166(2), 409-419.
91. Wang, F.; Schwarz, B.T.; Graham, W.V.; Wang, Y.; Su, L.; Clayburgh, D.R.; Abraham, C.; Turner, J.R. IFN-gamma-induced TNFR2 expression is required for TNF-dependent intestinal epithelial barrier dysfunction. Gastroenterology, 2006, 131(4), 1153-1163.
92. Al-Sadi, R.M.; Ma, T.Y. IL-1beta causes an increase in intestinal epithelial tight junction permeability. J. Immunol., 2007, 178(7), 4641-4649.
93. Schwarz, B.T.; Wang, F.; Shen, L.; Clayburgh, D.R.; Su, L.; Wang, Y.; Fu, Y.X.; Turner, J.R. LIGHT signals directly to intestinal epithelia to cause barrier dysfunction via cytoskeletal and endocytic mechanisms. Gastroenterology, 2007, 132(7), 2383-2394.
94. Simonovic, I.; Rosenberg, J.; Koutsouris, A.; Hecht, G. Enteropathogenic Escherichia coli dephosphorylates and dissociates occludin from intestinal epithelial tight junctions. Cell. Microbiol., 2000, 2(4), 305-315.
95. Muza-Moons, M.M.; Schneeberger, E.E.; 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., 2004, 6(8), 783-793.
96. Tomson, F.L.; Koutsouris, A.; Viswanathan, V.K.; Turner, J.R.; Savkovic, S.D; Hecht, G. Differing roles of protein kinase C-zeta in disruption of tight junction barrier by enteropathogenic and enterohemorrhagic Escherichia coli. Gastroenterology, 2004, 127(3), 859-869.
97. Malladi, V.; Shankar, B.; Williams, P.H.; Balakrishnan, A. Enteropathogenic Escherichia coli outer membrane proteins induce changes in cadherin junctions of Caco-2 cells through activation of PKCalpha. Microbes. Infect., 2004, 6(1), 38-50.
98. Savkovic, S.D.; Ramaswamy, A.; Koutsouris, A.; Hecht, G. EPECactivated ERK1/2 participate in inflammatory response but not tight junction barrier disruption. Am. J. Physiol. Gastrointest. Liver. Physiol., 2001, 281(4), G890-G898.
99. Viswanathan, V.K.; Weflen, A.; Koutsouris, A.; Roxas, J.L.; Hecht, G. Enteropathogenic E. coli-induced barrier function alteration is not a consequence of host cell apoptosis. Am. J. Physiol. Gastrointest. Liver Physiol., 2008, 294(5), G1165-G1170.
100. Li, Q.; Zhang, Q.; Wang, C.; Li, N.; Li, J. Invasion of enteropathogenic Escherichia coli into host cells through epithelial tight junctions. FEBS J., 2008, 275, 6022-6032.
101. Qin, H.; Zhang, Z.; Hang, X.; Jiang, Y. L. plantarum prevents Enteroinvasive Escherichia coli-induced tight junction proteins changes in intestinal epithelial cells. BMC Microbiology, 2009, 9, 63.
102. Dahan, S.; Dalmasso, G.; Imbert, V.; Peyron, J.F.; Rampal, P.; Czerucka, D. Saccharomyces boulardii interferes with enterohemorrhagic Escherichia coli-induced signaling pathways in T84 cells. Infect. Immun., 2003, 71(2), 766-773.
103. Zareie, M.; Riff, J.; Donato, K.; McKay, D.M.; Perdue, M.H.; Soderholm, J.D.; Karmali, M.; Cohen, M.B.; Hawkins, J.; Sherman, P.M. Novel effects of the prototype translocating Escherichia coli, strain C25 on intestinal epithelial structure and barrier function. Cell. Microbiol., 2005, 7(12), 1782-1797.
104. Nazli, A.; Yang, P.C.; Jury, J.; Howe, K.; Watson, J.L.; Soderholm, J.D.; Sherman, P.M.; Perdue, M.H.; McKay, D.M. Epithelia under metabolic stress perceive commensal bacteria as a threat. Am. J. Pathol., 2004, 164(3), 947-957.
105. Lewis, K.; Caldwell, J.; Phan, V.; Prescott, D.; Nazli, A.; Wang, A.; Soderhölm, J.D.; Perdue, M.H.; Sherman, P.M.; McKay, D.M. Decreased epithelial barrier function evoked by exposure to metabolic stress and nonpathogenic E. coli is enhanced by TNF-alpha. Am. J. Physiol. Gastrointest. Liver Physiol., 2008, 294(3), G669-G678.
106. Chen Ming, L.; Zhongming, G.; Fox, J.G.; Schauer, D.B. Disruption of tight junctions and induction of proinflammatory cytokine responses in colonic epithelial cells by Campylobacter jejuni. Infect. Immunity, 2006, 74(12), 6581-6589.
107. Lamb-Rosteski, J.M.; Kalischuk, L.D.; Inglis, G.D.; Buret, A.G. Epidermal growth factor inhibits Campylobacter jejuni-induced claudin-4 disruption, loss of epithelial barrier function, and Escherichia coli translocation. Infect. Immun., 2008, 76(8), 3390-3398.
108. Rees, L.E.; Cogan, T.A.; Dodson, A.L.; Birchall, M.A.; Bailey, M.; Humphrey, T.J. Campylobacter and IFNgamma interact to cause a rapid loss of epithelial barrier integrity. Inflamm. Bowel Dis., 2008, 14(3), 303-309.
109. Chen, M.L.; Pothoulakis, C.; 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., 2002, 277(6), 4247-4254.
110. Johal, S.S.; Solomon, K.; Dodson, S.; Borriello, S.P.; Mahida, Y.R. Differential effects of varying concentrations of Clostridium difficile toxin a on epithelial barrier function and expression of cytokines. J. Infect. Dis., 2004, 189(11), 2110-2119.
111. Fukazawa, A.; Alonso, C.; Kurachi, K.; Gupta, S.; Lesser, C.F.; McCormick, B.A.; Reinecker, H.C. GEF-H1 mediated control of NOD1 dependent NF-kB activation by shigella effectors. PLoS Pathog., 2008, 4(11), e1000228.
112. Shifflett, D.E.; Clayburgh, D.R.; Koutsouris, A.; Turner, J.R.; Hecht, G.A. Enteropathogenic E. coli disrupts tight junction barrier function and structure in vivo. Lab. Invest., 2005, 85(10), 1308-1324.
113. Li, Q.; Zhang, Q.; Wang, C.; Liu, X.; Li, N.; Li, J. Disruption of tight junctions during polymicrobial sepsis in vivo. J Pathol., 2009, 218(2), 210-221.
114. Moriez, R.; Leveque, M.; Salvador-Cartier, C.; Barreau, F.; Theodorou, V.; Fioramonti, J.; Bueno, L.; Eutamene, H. Mucosal mast cell proteases are involved in colonic permeability alterations and subsequent bacterial translocation in endotoxemic rats. Shock, 2007, 28(1), 118-124.
115. Clemente, M.G.; De Virgilis, S.; Kang, J.S.; Macatagney, R.; Musu, M.P.; Di Pierro, M.R.; Drago, S.; Congia, M.; Fasano, A. Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut, 2003, 52(2), 218-223.
116. Tripathi, A.; Lammers, K.M.; Goldblum, S.; Shea-Donohue, T.; Netzel-Arnett, S.; Buzza, M.S.; Antalis, T.M.; Vogel, S.N.; Zhao, A.; Yang, S.; Arrietta, M.C.; Meddings, J.B.; Fasano, A. Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc. Natl. Acad. Sci. USA, 2009, 106(39), 16799-16804.
117. El Asmar, R.; Panigrahi, P.; Bamford, P.; Berti, I.; Not, T.; Coppa, G.V.; Catassi, C.; Fasano, A. Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure. Gastroenterology, 2002, 123(5), 1607-1615.
118. Sander, G.R.; Cummins, A.G.; Henshall, T.; Powell, B.C. Rapid disruption of intestinal barrier function by gliadin involves altered expression of apical junctional proteins. FEBS Lett., 2005, 579(21), 4851-4855.
119. Drago, S.; El Asmar, R.; Di Pierro, M.; Grazia Clemente, M.; Tripathi, A.; Sapone, A.; Thakar, M.; Iacono, G.; Carroccio, A.; D'Agate, C.; Not, T.; Zampini, L.; Catassi, C.; Fasano, A. Gliadin; zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand. J. Gastroenterol., 2006, 41(4), 408-419.
120. 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.; Fasano, A. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology, 2008, 135(1), 194-204.
121. Ma, T.Y.; Nguyen, D.; Bui, V.; Nguyen, H.; Hoa, N. Ethanol modulation of intestinal epithelial tight junction barrier. Am. J. Physiol., 1999, 276(4pt1), G965-G974.
122. Catalioto, R.-M.; Festa, C.; Triolo, A.; Altamura, M.; Maggi, C.A.; Giuliani, S. Differential effect of ethanol and hydrogen peroxide on barrier function and prostaglandin E2 release in differentiated Caco-2 cells: Selective prevention by growth factors. J. Pharm. Sci., 2009, 98(2), 713-727.
123. Banan, A.; Choudhary, S.; Zhang, Y.; Fields, J.Z.; Keshavarzian, A. Ethanol-induced barrier dysfunction and its prevention by growth factors in human intestinal monolayers: Evidence for oxidative and cytoskeletal mechanisms. J. Pharmacol. Exp. Ther., 1999, 291(3), 1075-1085.
124. Banan, A.; Choudhary, S.; Zhang, Y.; Fields, J.Z.; Keshavarzian, A. Oxidant-induced intestinal barrier disruption and its prevention by growth factors in a human colonic cell line: Role of the microtubule cytoskeleton. Free Radic. Biol. Med., 2000, 28(5), 727-738.
125. Tang, Y.; Forsyth, C.B.; Farhadi, A.; Rangan, J.; Jakate, S.; Shaikh, M.; Banan, A.; Fields, J.Z.; Keshavarzian, A. Nitric oxide mediated intestinal injury is required for alcohol-induced gut leakiness and liver damage. Alcohol. Clin. Exp. Res., 2009, 33(7), 1220-1230.
126. Fisher, S.J.; Swaan, P.W.; Eddington, N.D. The ethanol metabolite acetaldehyde increases paracellular drug permeability in vitro and oral bioavailability in vivo. J. Pharmacol. Exp. Ther., 2010, 332(1), 326-333.
127. Sheth, P.; Seth, A.; Thangavel, M.; Basuroy, S.; Rao, R.K. Epidermal growth factor prevents acetaldehyde-induced paracellular permeability in Caco-2 cell monolayer. Alcohol Clin. Exp. Res., 2004, 28(5), 797-804. (Pubitemid 38661379)
128. Basuroy, S.; Sheth, P.; Mansbach, C.M.; Rao, R.K. Acetaldehyde disrupts tight junctions and adherens junctions in human colonic mucosa: Protection by EGF and L-glutamine. Am. J. Physiol. Gastrointest. Liver Physiol., 2005, 289, G367-G375.
129. Tang, Y.; Banan, A.; Forsyth, C.B.; Fields, J.Z.; Lau, C.K.; Zhang, L.J.; Keshavarzian, A. Effect of alcohol on miR-212 expression in intestinal epithelial cells and its potential role in alcoholic liver disease. Alcohol Clin. Exp. Res., 2008, 32(2), 355-364.
130. Ferrier, L.; Bérard, F.; Debrauwer, L.; Chabo, C.; Langella, P.; Buéno, L.; Fioramonti, J. Impairment of the intestinal barrier by ethanol involves enteric microflora and mast cell activation in rodents. Am. J. Pathol., 2006, 168(4), 1148-1154.
131. Dokladny, K.; Moseley, P.L.; Ma, T.Y. Physiologically relevant increase in temperature causes an increase in intestinal epithelial tight junction permeability. Am. J. Physiol. Gastrointest. Liver. Physiol., 2006, 290(2), G204-G212.
132. Yang, P.C.; He, S.H.; Zheng, P.Y. Investigation into the signal transduction pathway via which heat stress impairs intestinal epithelial barrier function. J. Gastroenterol. Hepatol., 2007, 22(11), 1823-1831.
133. Németh, Z.H.; Deitch, E.A.; Szabó, C.; Haskó, G. Hyperosmotic stress induces nuclear factor-kappaB activation and interleukin-8 production in human intestinal epithelial cells. Am. J. Pathol., 2002, 161(3), 987-996. (Pubitemid 34988386)
134. Yan, Y.; Dalmasso, G.; Nguyen, H.T.T.; Obertone, T.S.; Sitaraman, S.V.; Merlin, D. Ste20-related proline/alanine-rich kinase (spak) regulated transcriptionally by hyperosmolarity is involved in intestinal barrier function. PLoS One, 2009, 4(4), e5049.
135. Mazzon, E.; Sturniolo, G.C.; Puzzolo, D.; Frisina, N.; Fries, W. Effect of stress on the paracellular barrier in the rat ileum. Gut, 2002, 51(4), 507-513.
136. Mazzon, E.; Cuzzocrea, S. Role of TNF-alpha in ileum tight junction alteration in mouse model of restraint stress. Am. J. Physiol. Gastrointest. Liver Physiol., 2008, 294(5), G1268-G1280.
137. Demaude, J.; Levěque, M.; Chaumaz, G.; Eutaméne, H.; Fioramonti, J.; Bueno, L.; Ferrier, L. Acute stress increases colonic paracellular permeability in mice through a mast cell-independent mechanism: Involvement of pancreatic trypsin. Life Sci., 2009, 84(23-24), 847-852.
138. Ferrier, L.; Mazelin, L.; Cenac, N.; Desreumaux, P.; Janin, A.; Emilie, D.; Colombel, J.F.; Garcia-Villar, R.; Fioramonti, J.; Bueno, L. Stress-induced disruption of colonic epithelial barrier: Role of interferon-gamma and myosin light chain kinase in mice. Gastroenterology, 2003, 125(3), 795-804.
139. Cameron, H.L.; Perdue, M.H. Stress impairs murine intestinal barrier function: Improvement by glucagon-like peptide-2. J. Pharmacol. Exp. Ther., 2005, 314(1), 214-220.
140. Suenaert, P.; Bulteel, V.; Lemmens, L.; Noman, M.; Geypens, B.; Van Assche, G.; Geboes, K.; Ceuppens, J.L.; Rutgeerts, P. Anti- tumor necrosis factor treatment restores the gut barrier in Crohn's Disease. Am. J. Gastroenterol., 2002, 97(8), 2000-2004.
141. Banan, A.; Zhang, L.J.; Farhadi, A.; Fields, J.Z.; Shaikh, M.; Keshavarzian, A. PKC-beta1 isoform activation is required for EGF-induced NF-kappaB inactivation and IkappaBalpha stabilization and protection of F-actin assembly and barrier function in enterocyte monolayers. Am. J. Physiol. Cell. Physiol., 2004, 286(3), C723-C738.
142. Banan, A.; Zhang, L.J.; Shaikh, M.; Fields, J.Z.; Farhadi, A.; Keshavarzian, A. Inhibition of oxidant-induced nuclear factorkappaB activation and inhibitory-kappaBalpha degradation and instability of F-actin cytoskeletal dynamics and barrier function by epidermal growth factor: Key role of phospholipase-gamma isoform. J. Pharmacol. Exp. Ther., 2004, 309(1), 356-368.
143. Suzuki, T.; Seth, A.; Rao, R. Role of phospholipase C gammainduced activation of protein kinase Cepsilon (PKCepsilon) and PKCbetaI in epidermal growth factor-mediated protection of tight junctions from acetaldehyde in Caco-2 cell monolayers. J. Biol. Chem., 2008, 283(6), 3574-3583.
144. Buret, A.G.; Chin, A.C.; Scott, K.G. Infection of human and bovine epithelial cells with Cryptosporidium andersoni induces apoptosis and disrupts tight junctional ZO-1: Effects of epidermal growth factor. Int. J. Parasitol., 2003, 33(12), 1363-1371.
145. Clark, J.A.; Doelle, S.M.; Halpern, M.D.; Saunders, T.A.; Holubec, H.; Dvorak, K.; Boitano, S.A.; Dvorak, B. Intestinal barrier failure during experimental necrotizing enterocolitis: Protective effect of EGF treatment. Am. J. Physiol. Gastrointest. Liver. Physiol., 2006, 291(5), G938-G949.
146. Clark, J.A.; Gan, H.; Samocha, A.J.; Fox, A.C.; Buchman, T.G.; Coopersmith, C.M. Enterocyte-specific epidermal growth factor prevents barrier dysfunction and improves mortality in murine peritonitis. Am. J. Physiol. Gastrointest. Liver Physiol., 2009, 297(3), G471-G479.
147. Benjamin, M.A.; McKay, D.M.; Yang, P-C.; Cameron, H.; Perdue, M.H. Glucagon-like peptide-2 enhances intestinal epithelial barrier function of both transcellular and paracellular pathways in the mouse. Gut, 2000, 47(1), 112-119.
148. Kouris, G.J.; Liu, Q.; Rossi, H.; Djuricin, G.; Gattuso, P.; Nathan, C.; Weinstein, R.A.; Prinz, R.A. The effect of glucagon-like peptide 2 on intestinal permeability and bacterial translocation in acute necrotizing pancreatitis. Am. J. Surg., 2001, 181(6), 571-575.
149. Cameron, H.L.; Yang, P.-C.; Perdue, M.H. Glucagon-like peptide- 2-enhanced barrier function reduces pathophysiology in a model of food allergy. Am. J. Physiol. Gastrointest. Liver Physiol., 2003, 284, 905-912.
150. Kindon, H.; Pothoulakis, C.; Thim, L.; Lynch-Devaney, K.; Podolsky, D.K. Trefoil peptide protection of intestinal epithelial barrier function: Cooperative interaction with mucin glycoprotein. Gastroenterology, 1995, 109(2), 516-523.
151. Furuta, G.T.; Turner, J.R.; Taylor, C.T.; Hershberg, R.M.; Comerford, K.; Narravula, S.; Podolsky, D.K.; Colgan, S.P. Hypoxiainducible factor 1-dependent induction of intestinal trefoil factor protects barrier function during hypoxia. J. Exp. Med., 2001, 193(9), 1027-1034.
152. Meyer zum Büschenfelde, D.; Tauber, R.; Huber, O. TFF3-peptide increases transepithelial resistance in epithelial cells by modulating claudin-1 and -2 expression. Peptides, 2006, 27(12), 3383-3390.
153. Loncar, M.B.; Al-azzeh, E.D.; Sommer, P.S.; Marinovic, M.; Schmehl, K.; Kruschewski, M.; Blin, N.; Stohwasser, R.; Gött, P.; Kayademir, T. Tumour necrosis factor alpha and nuclear factor kappaB inhibit transcription of human TFF3 encoding a gastrointestinal healing peptide. Gut, 2003, 52(9), 1297-1303.
154. Song, M.; Xia, B.; Li, J. Effects of topical treatment of sodium butyrate and 5-aminosalicylic acid on expression of trefoil factor 3, interleukin 1beta, and nuclear factor kappaB in trinitrobenzene sulphonic acid induced colitis in rats. Postgrad. Med. J., 2006, 82(964), 130-135.
155. Teng, X.; Xu, L.-F.; Zhou, P.; Sun, H.-W.; Sun, M. Effects of Trefoil Peptide 3 on expression of TNF, TLR4, and NF-kB in trinitrobenzene sulphonic acid induced colitis mice. Inflammation, 2009, 32(2), 120-129.
156. Vandenbroucke, K.; Hans, W.; Van Huysse, J.; Neirynck, S.; Demetter, P.; Remaut, E.; Rottiers, P.; Steidler, L. Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice. Gastroenterology, 2004, 127(2), 502-513.
157. Ciacci, C.; Di Vizio, D.; Seth, R.; Insabato, G.; Mazzacca, G.; Podolsky, D.K.; Mahida, Y.R. Selective reduction of intestinal trefoil factor in untreated coeliac disease. Clin. Exp. Immunol., 2002, 130, 526-531.
158. Sinha, A.; Nightingale, J.; West, K.P.; Berlanga-Acosta, J.; Playford, R.J. Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis. N. Engl. J. Med., 2003, 349(4), 350-357.
159. Sigalet, D.L.; Martin, G.R.; Butzner, J.D.; Buret, A.; Meddings, J.B. A pilot study of the use of epidermal growth factor in pediatric short bowel syndrome. J. Pediatr. Surg., 2005, 40(5), 763-768.
160. Mahmood, A.; Melley, L.; Fitzgerald, A.J.; Ghosh, S.; Playford, R.J. Trial of trefoil factor 3 enemas, in combination with oral 5- aminosalicylic acid, for the treatment of mild-to-moderate leftsided ulcerative colitis. Aliment. Pharmacol. Ther., 2005, 21(11), 1357-1364.
161. Buchman, A.L.; Katz, S.; Fang, J.C.; Bernstein, C.N.; Abou-Assi, S.G.; Teduglutide Study Group. Teduglutide, a novel mucosally active analog of glucagon-like peptide-2 (GLP-2) for the treatment of moderate to severe Crohn's disease. Inflamm. Bowel. Dis., 2010, 16(6), 962-973.
162. Hamady, Z.Z.; Scott, N.; Farrar, M.D.; Lodge, J.P.; Holland, K.T.; Whitehead, T.; Carding, S.R. Xylan-regulated delivery of human keratinocyte growth factor-2 to the inflamed colon by the human anaerobic commensal bacterium Bacteroides ovatus. Gut., 2010, 59(4), 461-469.
163. Czerucka, D.; Dahan, S.; Mograbi, B.; Rossi, B.; Rampal, P. Saccharomyces boulardii preserves the barrier function and modulates the signal transduction pathway induced in enteropathogenic Escherichia coli-infected T84 cells. Infect. Immun., 2000, 68(10), 5998-6004.
164. Resta-Lenert, S.; Barrett, K.E. Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC). Gut, 2003, 52(7), 988-997.
165. Ko, J.S.; Yang, H.R.; Chang, J.Y.; Seo, J.K. Lactobacillus plantarum inhibits epithelial barrier dysfunction and interleukin-8 secretion induced by tumor necrosis factor-α. World J. Gastroenterol., 2007, 13(13), 1962-1965.
166. Johnson-Henry, K.C.; Donato, K.A.; Shen-Tu, G.; Gordanpour, M.; Sherman, P.M. Lactobacillus rhamnosus strain GG prevents enterohemorrhagic Escherichia coli O157:H7-induced changes in epithelial barrier function. Infect. Immun., 2008, 76(4), 1340-1348.
167. Seth, A.; Yan, F.; Polk, D.B.; Rao, R.K. Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKCand MAP kinase-dependent mechanism. Am. J. Physiol. Gastrointest. Liver Physiol., 2008, 294(4), G1060-G1069.
168. Ewaschuk, J.B.; Diaz, H.; Meddings, L.; Diederichs, B.; Dmytrash, A.; Backer, J.; Looijer-van Langen, M.; Madsen, K.L. Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. Am. J. Physiol. Gastrointest. Liver Physiol., 2008, 295, G1025-G1034.
169. Otte, J.M.; Podolsky, D.K. Functional modulation of enterocytes by gram-positive and gram-negative microorganisms. Am. J. Physiol. Gastrointest. Liver Physiol., 2004, 286(4), G613-G626.
170. Miyauchi, E.; Morita, H.; Okuda, J.; Sashihara, T.; Shimizu, M.; Tanabe, S. Cell wall fraction of Enterococcus hirae ameliorates TNF-alpha-induced barrier impairment in the human epithelial tight junction. Lett. Appl. Microbiol., 2008, 46(4), 469-476.
171. Bansal, T.; Alaniz, R.C.; Wood, T.K.; Jayaraman, A. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc. Natl. Acad. Sci. USA, 2010, 107(1), 228-233.
172. Lindfors, K.; Blomqvist, T.; Juuti-Uusitalo, K.; Stenman, S.; Venäläinen, J.; Mäki, M.; Kaukinen, K. Live probiotic Bifidobacterium lactis bacteria inhibit the toxic effects induced by wheat gliadin in epithelial cell culture. Clin. Exp. Immunol., 2008, 152, 552-558.
173. Forsyth, C.B.; Farhadi, A.; Jakate, S.M.; Tang, Y.; Shaikh, M.; Keshavarzian, A. Lactobacillus GG treatment ameliorates alcoholinduced intestinal oxidative stress, gut leakiness, and liver injury in a rat model of alcoholic steatohepatitis. Alcohol, 2009, 43(2), 163-172.
174. Lutgendorff, F.; Nijmeijer, R.M.; Sandström, P.A.; Trulsson, L.M.; Magnusson, K.E.; Timmerman, H.M.; van Minnen, L.P.; Rijkers, G.T.; Gooszen, H.G.; Akkermans, L.M.; Söderholm, J.D. Probiotics prevent intestinal barrier dysfunction in acute pancreatitis in rats via induction of ileal mucosal glutathione biosynthesis. PLoS One, 2009, 4(2), e4512.
175. Rychter, J.W.; van Minnen, L.P.; Verheem, A.; Timmerman, H.M.; Rijkers, G.T.; Schipper, M.E.; Gooszen, H.G.; Akkermans, L.M.; Kroese, A.B. Pretreatment but not treatment with probiotics abolishes mouse intestinal barrier dysfunction in acute pancreatitis. Surgery, 2009, 145(2), 157-167.
176. Mennigen, R.; Nolte, K.; Rijcken, E.; Utech, M.; Loeffler, B.; Senninger, N.; Bruewer, M. Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. Am. J. Physiol. Gastrointest. Liver Physiol., 2009, 296(5), G1140-G1149.
177. Madsen, K.; Cornish, A.; Soper, P.; McKaigney, C.; Jijon, H.; Yachimec, C.; Doyle, J.; Jewell, L.; De Simone, C. Probiotic bacteria enhance murine and human intestinal epithelial barrier function. Gastroenterology, 2001, 121(3), 580-591.
178. Ewaschuk, J.; Endersby, R.; Thiel, D.; Diaz, H.; Backer, J.; Ma, M.; Churchill, T.; Madsen, K. Probiotic bacteria prevent hepatic damage and maintain colonic barrier function in a mouse model of sepsis. Hepatology, 2007, 46(3), 841-850.
179. Pagnini, C.; Saeed, R.; Bamias, G.; Arseneau, K.O.; Pizarro, T.T.; Cominelli, F. Probiotics promote gut health through stimulation of epithelial innate immunity. Proc. Natl. Acad. Sci. USA, 2010, 107(1), 454-459.
180. Isaacs, K.; Herfarth, H. Role of probiotic therapy in IBD. Inflamm. Bowel. Dis., 2008, 14(11), 1597-1605.
181. Mimura, T.; Rizzello, F.; Helwig, U.; Poggioli, G.; Schreiber, S.; Talbot, I.C.; Nicholls, R.J.; Gionchetti, P.; Campieri, M.; Kamm, M.A. Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut, 2004, 53(1), 108-114.
182. Miele, E.; Pascarella, F.; Giannetti, E.; Quaglietta, L.; Baldassano, R.N.; Staiano, A. Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis. Am. J. Gastroenterol., 2009, 104(2), 437-443.
183. Sood, A.; Midha, V.; Makharia, G.K.; Ahuja, V.; Singal, D.; Goswami, P.; Tandon, R.K. The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin. Gastroenterol. Hepatol., 2009, 7(11), 1202-1209.
184. Tursi, A.; Brandimarte, G.; Papa, A.; Giglio, A.; Elisei, W.; Giorgetti, G.M.; Forti, G.; Morini, S.; Hassan, C.; Pistoia, M.A.; Modeo, M.E.; Rodino, S.; D'Amico, T.; Sebkova, L.; Sacca, N.; Di Giulio, E.; Luzza, F.; Imeneo, M.; Larussa, T.; Di Rosa, S.; Annese, V.; Danese, S.; Gasbarrini, A. Treatment of Relapsing Mildto- Moderate Ulcerative Colitis With the Probiotic VSL#3 as Adjunctive to a Standard Pharmaceutical Treatment: A Double-Blind, Randomized, Placebo-Controlled Study. Am. J. Gastroenterol., 2010, 105(10), 2218-2227.
185. Schultz, M. Clinical use of E. coli Nissle 1917 in inflammatory bowel disease. Inflamm. Bowel. Dis., 2008, 14(7), 1012-1018.
186. Vilela, G.E.; De Lourdes De Abreu Ferrari, M.; Oswaldo Da Gama Torres, H.; Guerra Pinto, A.; Carolina Carneiro Aguirre, A.; Paiva Martins, F.; Marcos Andrade Goulart, E.; Sales Da Cunha, A. Influence of Saccharomyces boulardii on the intestinal permeability ofpatients with Crohn's disease in remission. Scand. J. Gastroenterol., 2008, 43(7), 842-848.
187. Zeng, J.; Li, Y.Q.; Zuo, X.L.; Zhen, Y.B.; Yang, J.; Liu, C.H. Clinical trial: Effect of active lactic acid bacteria on mucosal barrier function in patients with diarrhoea-predominant irritable bowel syndrome. Aliment. Pharmacol. Ther., 2008, 28(8), 994-1002.
188. Qin, H.L.; Zheng, J.J.; Tong, D.N.; Chen, W.X.; Fan, X.B.; Hang, X.M.; Jiang, Y.Q. Effect of Lactobacillus plantarum enteral feeding on the gut permeability and septic complications in the patients with acute pancreatitis. Eur. J. Clin. Nutr., 2008, 62(7), 923-930.
189. Besselink, M.G.; van Santvoort, H.C.; Renooij, W.; de Smet, M.B.; Boermeester, M.A.; Fischer, K.; Timmerman, H.M.; Ahmed, A.U.; Cirkel, G.A.; Bollen, T.L.; van Ramshorst, B.; Schaapherder, A.F.; Witteman, B.J.; Ploeg, R.J.; van Goor, H.; van Laarhoven, C.J.; Tan, A.C.; Brink, M.A.; van der Harst, E.; Wahab, P.J.; van Eijck, C.H.; Dejong, C.H.; van Erpecum, K.J.; Akkermans, L.M.; Gooszen, H.G. Dutch Acute Pancreatitis Study Group. Intestinal Barrier Dysfunction in a Randomized Trial of a specific probiotic composition in acute pancreatitis. Ann. Surg., 2009, 250(5), 712-719.
190. Besselink, M.G.H.; van Santvoort, H.C.; Buskens, E.; Boermeester, M.A.; van Goor, H.; Timmerman, H.M.; Nieuwenhuijs, V.B.; Bollen, T.L.; van Ramshorst, B.; Witteman, B.J.M.; Rosman, C.; Ploeg, R.J.; Brink, M.A.; Schaapherder, A.F.M.; Dejong, C.H.C.; Wahab, P.J.; van Laarhoven, C.J.H.M.; van der Harst, E.; van Eijck, C.H.J.; Cuesta, M.A.; Akkermans, L.M.A.; Gooszen, H.G. Probiotic prophylaxis in predicted severe acute pancreatitis: A randomised, double-blind, placebo-controlled trial. Lancet, 2008, 371(9613), 651-659.
191. Al-Sadi, R.; Ye, D.; Dokladny, K.; Ma, T.Y. Mechanism of Il- 1{beta}-induced increase in intestinal epithelial tight junction permeability. J. Immunol., 2008, 180, 5653-5661.
192. Ye, D.; Ma, I.; Ma, T.Y. Molecular mechanism of tumor necrosis factor- modulation of intestinal epithelial tight junction barrier. Am. J. Physiol. Gastrointest. Liver Physiol., 2006, 290(3), G496-G504.
193. Boivin, M.A.; Roy, P.K.; Bradley, A.; Kennedy, J.C.; Rihani, T.; Ma, T.Y. Mechanism of interferon-gamma-induced increase in T84 intestinal epithelial tight junction. J. Interferon. Cytokine. Res., 2009, 29(1), 45-54.
194. Banan, A.; Farhadi, A.; Fields, J.Z.; Mutlu, E.; Zhang, L.; Keshavarzian, A. Evidence that nuclear factor-kappa B activation is critical in oxidant-induced disruption of the microtubule cytoskeleton and barrier integrity and that its inactivation is essential in epidermal growth factor-mediated protection of the monolayers of intestinal epithelia. J. Pharmacol. Exp. Ther., 2003, 306(1), 13-28.
195. Banan, A.; Keshavarzian, A.; Zhang, L.; Shaikh, M.; Forsyth, C.B.; Tang, Y.; Fields, J.Z. NF-kappaB activation as a key mechanism in ethanol-induced disruption of the F-actin cytoskeleton and monolayer barrier integrity in intestinal epithelium. Alcohol, 2007, 41(6), 447-460.
196. Németh, Z.H.; Deitch, E.A.; Davidson, M.T.; Szabó, C.; Vizi, E.S.; Haskó, G. Disruption of the actin cytoskeleton results in nuclear factor-kappaB activation and inflammatory mediator production in cultured human intestinal epithelial cells. J. Cell. Physiol., 2004, 200(1), 71-81.
197. Sougioultzis, S.; Simeonidis, S.; Bhaskar, K.R.; Chen, X.; Anton, P.M.; Keates, S.; Pothoulakis, C.; Kelly, C.P. Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF- B-mediated IL-8 gene expression. Biochem. Biophys. Res. Commun., 2006, 343(1), 69-76.
198. Zhou, W.; Cao, Q.; Peng, Y.; Zhang, Q.J.; Castrillon, D.H.; De- Pinho, R.A.; Liu, Z.P. FoxO4 inhibits NF-kappaB and protects mice against colonic injury and inflammation. Gastroenterology, 2009, 137(4),1403-1414.
199. Blair, S.A.; Kane, S.V.; Clayburgh, D.R.; Turner, J.R. Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease. Lab. Invest., 2006, 86(2), 191-201.
200. Zolotarevsky, Y.; Hecht, G.; Koutsouris, A.; Gonzalez, D.E.; Quan, C.; Tom, J.; Mrsny, R.J.; Turner, J.R. A membrane-permeant peptide that inhibits MLC kinase restores barrier function in in vitro models of intestinal disease. Gastroenterology, 2002, 123(1), 163-172.
201. Ma, T.Y.; Boivin, M.A.; Ye, D.; Pedram, A.; Said, H.M. Mechanism of TNF-{alpha} modulation of Caco-2 intestinal epithelial tight junction barrier: Role of myosin light-chain kinase protein expression. Am. J. Physiol. Gastrointest. Liver Physiol., 2005, 288(3), G422-G430.
202. Ye, D.; Ma, T.Y. Cellular and molecular mechanisms that mediate basal and tumour necrosis factor-alpha-induced regulation of myosin light chain kinase gene activity. J. Cell. Mol. Med., 2008, 12(4), 1331-1346.
203. Boivin, M.A.; Ye, D.; Kennedy, J.C.; Al-Sadi, R.; Shepela, C.; Ma, T.Y. Mechanism of glucocorticoid regulation of the intestinal tight junction barrier. Am. J. Physiol. Gastrointest. Liver Physiol., 2007, 292(2), G590-G598.
204. Clayburgh, D.R.; Musch, M.W.; Leitges, M.; Fu, Y.X.; Turner, J.R. Coordinated epithelial NHE3 inhibition and barrier dysfunction are required for TNF-mediated diarrhea in vivo. J. Clin. Invest., 2006, 116(10), 2682-2694.
205. Clayburgh, D.R.; Barrett, T.A.; Tang, Y.; Meddings, J.B.; Van Eldik, L.J.; Watterson, D.M.; Clarke, L.L.; Mrsny, R.J.; Turner, J.R. Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo. J. Clin. Invest., 2005, 115(10), 2702-2715.
206. Moriez, R.; Salvador-Cartier, C.; Theodorou, V.; Fioramonti, J.; Eutamene, H.; Bueno, L. Myosin light chain kinase is involved in lipopolysaccharide-induced disruption of colonic epithelial barrier and bacterial translocation in rats. Am. J. Pathol., 2005, 167(4), 1071-1079.
207. Weber, C.R.; Raleigh, D.R.; Su, L.; Shen, L.; Sullivan, E.A.; Wang, Y.; Turner, J.R. Epithelial myosin light chain kinase activation induces mucosal interleukin-13 expression to alter tight junction ion selectivity. J. Biol. Chem., 2010, 285(16), 12037-12046.
208. Yamada, R.; Seto, M. 5-Substituted isoquinoline drugs. JP-2005232175, September 02, 2005.
209. Yamada, R.; Seto, M. Nitrogeneous tricyclic compound. WO-2006057270, June 01, 2006.
210. Yamada, R.; Seto, M. Sulfonamide compound. WO-2007026664, March 8, 2007.
211. Kida, H.; Matsubara, K.; Kaneko, S.; Kanzawa; Y. Sulfonamide compound, and crystal thereof. WO-2009004792, January 8, 2009.
212. Plettenburg, O.; Hofmeister, A.; Kadereit, D.; Brendel, J.; Loehn, M.. Cyclohexylamin isoquinolone derivatives as Rho-kinase inhibitors. WO-2007012422, February 01, 2007.
213. Plettenburg, O.; Hofmeister, A.; Kadereit, D.; Brendel, J.; Loehn, M.. Piperidinyl-substituted isoquinolone derivatives as Rho-kinase inhibitors. WO-2007012421, February 01, 2007.
214. Plettenburg, O.; Hofmeister, A.; Kadereit, D.; Peukert, S.; Ruf, S.; Ritter, K.; Löhn, M.; Ivashchenko, Y.; Monecke, P.; Dreyer, M.; Kannt, A.. Isoquinoline derivatives as inhibitors of rho-kinase. WO-2007000240, January 04, 2007.
215. Watterson, D.M.; Van Eldik, L.J.; Behanna, H.; Ranaivo, Hantamalala, Ralay. Myosin light chain kinase inhibitor compounds, compositions and related methods of use. WO-2008011176, January 24, 2008.
216. Cenac, N.; Chin, A.C.; Garcia-Villar, R.; Salvador-Cartier, C.; Ferrier, L.; Vergnolle, N.; Buret, A.G.; Fioramonti, J.; Bueno, L. PAR2 activation alters colonic paracellular permeability in mice via IFN-gamma-dependent and -independent pathways. J. Physiol., 2004, 558(Pt 3), 913-925.
217. Jacob, C.; Yang, P.-C.; Darmoul, D.; Amadesi, S.; Saito, T.; Cottrell, G.S.; Coelho, A.-M.; Singh, P.; Grady, E.F.; Perdue, M.; Bunnett, N.W. Mast Cell Tryptase Controls Paracellular Permeability of the Intestine. Role of protease activated receptor 2 and β- arrestins. J. Biol. Chem., 2005, 280(36), 31936-31948.
218. Cenac, N.; Coelho, A.M.; Nguyen, C.; Compton, S.; Andrade- Gordon, P.; MacNaughton, W.K.; Wallace, J.L.; Hollenberg, M.D.; Bunnett, N.W.; Garcia-Villar, R.; Bueno, L.; Vergnolle, N. Induction of intestinal inflammation in mouse by activation of proteinase- activated receptor-2. Am. J. Pathol., 2002, 161(5), 1903-1915.
219. Cenac, N.; Garcia-Villar, R.; Ferrier, L.; Larauche, M.; Vergnolle, N.; Bunnett, N.W.; Coelho, A.M.; Fioramonti, J.; Bueno, L. Proteinase- activated receptor-2-induced colonic inflammation in mice: Possible involvement of afferent neurons, nitric oxide, and paracellular permeability. J. Immunol., 2003, 170(8), 4296-4300.
220. Róka, R.; Ait-Belgnaoui, A.; Salvador-Cartier, C.; Garcia-Villar, R.; Fioramonti, J.; Eutaméne, H.; Bueno, L. Dexamethasone prevents visceral hyperalgesia but not colonic permeability increase induced by luminal protease-activated receptor-2 agonist in rats. Gut, 2007, 56(8), 1072-1078.
221. Róka, R.; Demaude, J.; Cenac, N.; Ferrier, L.; Salvador-Cartier, C.; Garcia-Villar, R.; Fioramonti, J.; Bueno, L. Colonic luminal proteases activate colonocyte proteinase-activated receptor-2 and regulate paracellular permeability in mice. Neurogastroenterol. Motil., 2007, 19(1), 57-65.
222. Chin, A.C.; Lee, W.Y.; Nusrat, A.; Vergnolle, N.; Parkos, C.A. Neutrophil-mediated activation of epithelial protease-activated receptors- 1 and -2 regulates barrier function and transepithelial migration. J. Immunol., 2008, 181(8), 5702-5710.
223. Santos, J.; Yang, P.C.; Söderholm, J.D.; Benjamin, M.; Perdue, M.H. Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat. Gut, 2001, 48(5), 630-636.
224. Cottrell, G.S.; Amadesi, S.; Pikios, S.; Camerer, E.; Willardsen, J.A.; Murphy, B.R.; Caughey, G.H.; Wolters, P.J.; Coughlin, S.R.; Peterson, A.; Knecht, W.; Pothoulakis, C.; Bunnett, N.W.; Grady, E.F. Protease-activated receptor 2; dipeptidyl peptidase I; and proteases mediate clostridium difficile toxin A enteritis. Gastroenterology, 2007, 132, 2422-2437.
225. Kerckhoffs, A.P.; Ter Linde, J.J.; Akkermans, L.M.; Samsom, M. Trypsinogen IV; serotonin transporter transcript levels and serotonin content are increased in small intestine of irritable bowel syndrome patients. Neurogastroenterol. Motil., 2008, 20(8), 900-907.
226. Lee, J.W.; Park, J.H.; Park, D.I.; Park, J.H.; Kim, H.J.; Cho, Y.K.; Sohn, C.I.; Jeon, W.K.; Kim, B.I. Subjects with diarrheapredominant IBS have increased rectal permeability responsive to tryptase. Dig. Dis. Sci., 2010, 55(10), 2922-2928.
227. Kanke, T.; Kabeya, M.; Kubo, S.; Kondo, S.; Yasuoka, K.; Tagashira, J.; Ishiwata, H.; Saka, M.; Furuyama, T.; Nishiyama, T.; Doi, T.; Hattori, Y.; Kawabata, A.; Cunningham, M.R.; Plevin, R. Novel antagonists for proteinase-activated receptor 2: Inhibition of cellular and vascular responses in vitro and in vivo. Br. J. Pharmacol., 2009, 158(1), 361-371.
228. Goh, F.G.; Ng, P.Y.; Nilsson, M.; Kanke, T.; Plevin, R. Dual effect of the novel peptide antagonist K-14585 on proteinase-activated receptor- 2-mediated signalling. Br. J. Pharmacol., 2009, 158(7), 1695-1704.
229. Virca, G.D.; Hu, S.-F.S. Antibodies that bind PAR-2. WO-2007092640, August 16, 2007.
230. Virca, G.D.; Hu, S.-F.S. Antigen-binding proteins that bind PAR-2. WO-2009005726, January 08, 2009.
231. Paterson, B.M.; Lammers, K.M.; Arrieta, M.C.; Fasano, A.; Meddings, J.B. The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: A proof of concept study. Aliment. Pharmacol. Ther., 2007, 26(5), 757-766.
232. Arrieta, M.C.; Madsen, K.; Doyle, J.; Meddings, J. Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouse. Gut, 2009, 58(1), 41-48.
233. Tamiz, A. Novel short peptides that inhibit the opning of mammalian tight junctions. WO-2008150981, Dicember 11, 2008.
234. Tamiz, A. Novel inhibitors of mammalian tight junction opening. WO-2009052489, April 23, 2009.