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Gastroenterology Research and Practice
Volume 2016, Article ID 7374197, 9 pages
http://dx.doi.org/10.1155/2016/7374197
Review Article

Crosstalk between Inflammation and ROCK/MLCK Signaling Pathways in Gastrointestinal Disorders with Intestinal Hyperpermeability

1Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
2Division of Gastroenterology, Loma Linda University, Loma Linda, CA, USA
3Department of Gastroenterology, Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang Province, China

Received 24 April 2016; Revised 12 July 2016; Accepted 19 July 2016

Academic Editor: Jean-Francois Beaulieu

Copyright © 2016 Lijun Du et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. L. Shen and J. R. Turner, “Role of epithelial cells in initiation and propagation of intestinal inflammation. Eliminating the static: tight junction dynamics exposed,” American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 290, no. 4, pp. G577–G582, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. S. Tsukita, M. Furuse, and M. Itoh, “Multifunctional strands in tight junctions,” Nature Reviews Molecular Cell Biology, vol. 2, no. 4, pp. 285–293, 2001. View at Publisher · View at Google Scholar · View at Scopus
  3. A. S. Gehren, M. R. Rocha, W. F. de Souza, and J. A. Morgado-Díaz, “Alterations of the apical junctional complex and actin cytoskeleton and their role in colorectal cancer progression,” Tissue Barriers, vol. 3, no. 3, Article ID e1017688, 2015. View at Publisher · View at Google Scholar
  4. E. Dejana, “Endothelial cell-cell junctions: happy together,” Nature Reviews Molecular Cell Biology, vol. 5, no. 4, pp. 261–270, 2004. View at Publisher · View at Google Scholar · View at Scopus
  5. K. Matter and M. S. Balda, “Signalling to and from tight junctions,” Nature Reviews Molecular Cell Biology, vol. 4, no. 3, pp. 225–236, 2003. View at Publisher · View at Google Scholar · View at Scopus
  6. R.-M. Mège, J. Gavard, and M. Lambert, “Regulation of cell-cell junctions by the cytoskeleton,” Current Opinion in Cell Biology, vol. 18, no. 5, pp. 541–548, 2006. View at Publisher · View at Google Scholar · View at Scopus
  7. A. Nusrat, J. R. Turner, and J. L. Madara, “Molecular physiology and pathophysiology of tight junctions. IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells,” American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 279, no. 5, pp. G851–G857, 2000. View at Google Scholar · View at Scopus
  8. A. I. Ivanov, D. Hunt, M. Utech, A. Nusrat, and C. A. Parkos, “Differential roles for actin polymerization and a myosin II motor in assembly of the epithelial apical junctional complex,” Molecular Biology of the Cell, vol. 16, no. 6, pp. 2636–2650, 2005. View at Publisher · View at Google Scholar · View at Scopus
  9. N. G. Naydenov, A. Feygin, D. Wang et al., “Nonmuscle myosin IIA regulates intestinal epithelial barrier in vivo and plays a protective role during experimental colitis,” Scientific Reports, vol. 6, Article ID 24161, 2016. View at Publisher · View at Google Scholar
  10. M. Vicente-Manzanares, X. Ma, R. S. Adelstein, and A. R. Horwitz, “Non-muscle myosin II takes centre stage in cell adhesion and migration,” Nature Reviews Molecular Cell Biology, vol. 10, no. 11, pp. 778–790, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. S. M. Heissler and D. J. Manstein, “Nonmuscle myosin-2: mix and match,” Cellular and Molecular Life Sciences, vol. 70, no. 1, pp. 1–21, 2013. View at Publisher · View at Google Scholar · View at Scopus
  12. R. S. Adelstein, “Calmodulin and the regulation of the actin-myosin interaction in smooth muscle and nonmuscle cells,” Cell, vol. 30, no. 2, pp. 349–350, 1982. View at Publisher · View at Google Scholar · View at Scopus
  13. M. Amano, M. Ito, K. Kimura et al., “Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase),” The Journal of Biological Chemistry, vol. 271, no. 34, pp. 20246–20249, 1996. View at Publisher · View at Google Scholar · View at Scopus
  14. S. Komatsu and M. Ikebe, “ZIP kinase is responsible for the phosphorylation of myosin II and necessary for cell motility in mammalian fibroblasts,” Journal of Cell Biology, vol. 165, no. 2, pp. 243–254, 2004. View at Publisher · View at Google Scholar · View at Scopus
  15. S. Yamashiro, G. Totsukawa, Y. Yamakita et al., “Citron kinase, a Rho-dependent kinase, induces di-phosphorylation of regulatory light chain of myosin II,” Molecular Biology of the Cell, vol. 14, no. 5, pp. 1745–1756, 2003. View at Publisher · View at Google Scholar · View at Scopus
  16. Y. Zolotarevsky, G. Hecht, A. Koutsouris et al., “A membrane-permeant peptide that inhibits MLC kinase restores barrier function in in vitro models of intestinal disease,” Gastroenterology, vol. 123, no. 1, pp. 163–172, 2002. View at Publisher · View at Google Scholar · View at Scopus
  17. A. Nusrat, M. Giry, J. R. Turner et al., “Rho protein regulates tight junctions and perijunctional actin organization in polarized epithelia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 23, pp. 10629–10633, 1995. View at Publisher · View at Google Scholar · View at Scopus
  18. T. Y. Ma, D. Tran, N. Hoa, D. Nguyen, M. Merryfield, and A. Tarnawski, “Mechanism of extracellular calcium regulation of intestinal epithelial tight junction permeability: role of cytoskeletal involvement,” Microscopy Research and Technique, vol. 51, no. 2, pp. 156–168, 2000. View at Publisher · View at Google Scholar · View at Scopus
  19. S. Yang, M. Yu, L. Sun et al., “Interferon-γ-induced intestinal epithelial barrier dysfunction by NF-κB/HIF-1α pathway,” Journal of Interferon & Cytokine Research, vol. 34, no. 3, pp. 195–203, 2014. View at Publisher · View at Google Scholar · View at Scopus
  20. H. Liu, P. Wang, and F.-J. Wang, “An experimental study on intestinal epithelial barrier dysfunction induced by interferon-gamma and tumor necrosis factor-alpha,” Chinese Journal of Burns, vol. 27, no. 2, pp. 145–149, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. R. Al-Sadi, D. Ye, K. Dokladny, and T. Y. Ma, “Mechanism of IL-1β-induced increase in intestinal epithelial tight junction permeability,” The Journal of Immunology, vol. 180, no. 8, pp. 5653–5661, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. F. He, J. Peng, X.-L. Deng et al., “Mechanisms of tumor necrosis factor-alpha-induced leaks in intestine epithelial barrier,” Cytokine, vol. 59, no. 2, pp. 264–272, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. T. Suzuki, N. Yoshinaga, and S. Tanabe, “Interleukin-6 (IL-6) regulates claudin-2 expression and tight junction permeability in intestinal epithelium,” Journal of Biological Chemistry, vol. 286, no. 36, pp. 31263–31271, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. F. Heller, P. Florian, C. Bojarski et al., “Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution,” Gastroenterology, vol. 129, no. 2, pp. 550–564, 2005. View at Publisher · View at Google Scholar · View at Scopus
  25. D. R. Clayburgh, L. Shen, and J. R. Turner, “A porous defense: the leaky epithelial barrier in intestinal disease,” Laboratory Investigation, vol. 84, no. 3, pp. 282–291, 2004. View at Publisher · View at Google Scholar · View at Scopus
  26. E. Wilcz-Villega, S. McClean, and M. O'Sullivan, “Reduced E-cadherin expression is associated with abdominal pain and symptom duration in a study of alternating and diarrhea predominant IBS,” Neurogastroenterology and Motility, vol. 26, no. 3, pp. 316–325, 2014. View at Publisher · View at Google Scholar · View at Scopus
  27. H. Vanheel, M. Vicario, T. Vanuytsel et al., “Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia,” Gut, vol. 63, no. 2, pp. 262–271, 2014. View at Publisher · View at Google Scholar · View at Scopus
  28. C. R. Hedin, N. E. McCarthy, P. Louis et al., “Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings,” Gut, vol. 63, no. 10, pp. 1578–1586, 2014. View at Publisher · View at Google Scholar · View at Scopus
  29. G. Tolstanova, X. Deng, S. W. French et al., “Early endothelial damage and increased colonic vascular permeability in the development of experimental ulcerative colitis in rats and mice,” Laboratory Investigation, vol. 92, no. 1, pp. 9–21, 2012. View at Publisher · View at Google Scholar · View at Scopus
  30. J. R. Turner, B. K. Rill, S. L. Carlson et al., “Physiological regulation of epithelial tight junctions is associated with myosin light-chain phosphorylation,” The American Journal of Physiology, vol. 273, no. 4, pp. C1378–C1385, 1997. View at Google Scholar · View at Scopus
  31. K. G. E. Scott, J. B. Meddings, D. R. Kirk, S. P. Lees-Miller, and A. G. Buret, “Intestinal infection with Giardia spp. reduces epithelial barrier function in a myosin light chain kinase-dependent fashion,” Gastroenterology, vol. 123, no. 4, pp. 1179–1190, 2002. View at Publisher · View at Google Scholar · View at Scopus
  32. L. Van Aelst and C. D'Souza-Schorey, “Rho GTPases and signaling networks,” Genes & Development, vol. 11, no. 18, pp. 2295–2322, 1997. View at Publisher · View at Google Scholar · View at Scopus
  33. A. L. Bishop and A. Hall, “Rho GTPases and their effector proteins,” The Biochemical Journal, vol. 348, no. 2, pp. 241–255, 2000. View at Publisher · View at Google Scholar · View at Scopus
  34. K. L. Rossman, C. J. Der, and J. Sondek, “GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors,” Nature Reviews Molecular Cell Biology, vol. 6, no. 2, pp. 167–180, 2005. View at Publisher · View at Google Scholar · View at Scopus
  35. S. P. Ngok, W.-H. Lin, and P. Z. Anastasiadis, “Establishment of epithelial polarity—GEF who's minding the GAP?” Journal of Cell Science, vol. 127, no. 15, pp. 3205–3215, 2014. View at Publisher · View at Google Scholar · View at Scopus
  36. K. Riento and A. J. Ridley, “Rocks: multifunctional kinases in cell behaviour,” Nature Reviews Molecular Cell Biology, vol. 4, no. 6, pp. 446–456, 2003. View at Publisher · View at Google Scholar · View at Scopus
  37. A. Schmandke, A. Schmandke, and S. M. Strittmatter, “Reviews: ROCK and Rho: biochemistry and neuronal functions of Rho-associated protein kinases,” Neuroscientist, vol. 13, no. 5, pp. 454–469, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. S. V. Walsh, A. M. Hopkins, J. Chen, S. Narumiya, C. A. Parkos, and A. Nusrat, “Rho kinase regulates tight junction function and is necessary for tight junction assembly in polarized intestinal epithelia,” Gastroenterology, vol. 121, no. 3, pp. 566–579, 2001. View at Publisher · View at Google Scholar · View at Scopus
  39. Q.-Y. Lu, W. Chen, L. Lu, Z. Zheng, and X. Xu, “Involvement of RhoA/ROCK1 signaling pathway in hyperglycemia-induced microvascular endothelial dysfunction in diabetic retinopathy,” International Journal of Clinical and Experimental Pathology, vol. 7, no. 10, pp. 7268–7277, 2014. View at Google Scholar · View at Scopus
  40. M. Maekawa, T. Ishizaki, S. Boku et al., “Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase,” Science, vol. 285, no. 5429, pp. 895–898, 1999. View at Publisher · View at Google Scholar · View at Scopus
  41. J. R. Turner, “Intestinal mucosal barrier function in health and disease,” Nature Reviews Immunology, vol. 9, no. 11, pp. 799–809, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. A. D. Verin, V. Lazar, R. J. Torry, C. A. Labarrere, C. E. Patterson, and J. G. N. Garcia, “Expression of a novel high molecular-weight myosin light chain kinase in endothelium,” American Journal of Respiratory Cell and Molecular Biology, vol. 19, no. 5, pp. 758–766, 1998. View at Publisher · View at Google Scholar · View at Scopus
  43. D. R. Clayburgh, S. Rosen, E. D. Witkowski et al., “A differentiation-dependent splice variant of myosin light chain kinase, MLCK1, regulates epithelial tight junction permeability,” The Journal of Biological Chemistry, vol. 279, no. 53, pp. 55506–55513, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. A. Zahs, M. D. Bird, L. Ramirez, J. R. Turner, M. A. Choudhry, and E. J. Kovacs, “Inhibition of long myosin light-chain kinase activation alleviates intestinal damage after binge ethanol exposure and burn injury,” American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 303, no. 6, pp. G705–G712, 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. S. A. Blair, S. V. Kane, D. R. Clayburgh, and J. R. Turner, “Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease,” Laboratory Investigation, vol. 86, no. 2, pp. 191–201, 2006. View at Publisher · View at Google Scholar · View at Scopus
  46. C. Chen, P. Wang, Q. Su, S. Wang, and F. Wang, “Myosin light chain kinase mediates intestinal barrier disruption following burn injury,” PLoS ONE, vol. 7, no. 4, Article ID e34946, 2012. View at Publisher · View at Google Scholar · View at Scopus
  47. C. Martínez, B. Lobo, M. Pigrau et al., “Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier,” Gut, vol. 62, no. 8, pp. 1160–1168, 2013. View at Publisher · View at Google Scholar · View at Scopus
  48. T.-S. Jou, E. E. Schneeberger, and W. J. Nelson, “Structural and functional regulation of tight junctions by RhoA and Rac1 small GTPases,” Journal of Cell Biology, vol. 142, no. 1, pp. 101–115, 1998. View at Publisher · View at Google Scholar · View at Scopus
  49. J. Mankertz, S. Tavalali, H. Schmitz, A. Mankertz, E. O. Riecken, M. Fromm et al., “Expression from the human occludin promoter is affected by tumor necrosis factor alpha and interferon gamma,” Journal of Cell Science, vol. 113, part 11, pp. 2085–2090, 2000. View at Google Scholar
  50. G. Benais-Pont, A. Punn, C. Flores-Maldonado et al., “Identification of a tight junction-associated guanine nucleotide exchange factor that activates Rho and regulates paracellular permeability,” Journal of Cell Biology, vol. 160, no. 5, pp. 729–740, 2003. View at Publisher · View at Google Scholar · View at Scopus
  51. F. Wang, W. V. Graham, Y. Wang, E. D. Witkowski, B. T. Schwarz, and J. R. Turner, “Interferon-γ and tumor necrosis factor-α synergize to induce intestinal epithelial barrier dysfunction by up-regulating myosin light chain kinase expression,” The American Journal of Pathology, vol. 166, no. 2, pp. 409–419, 2005. View at Publisher · View at Google Scholar · View at Scopus
  52. G. Totsukawa, Y. Yamakita, S. Yamashiro, D. J. Hartshorne, Y. Sasaki, and F. Matsumura, “Distinct roles of ROCK (Rho-kinase) and MLCK in spatial regulation of MLC phosphorylation for assembly of stress fibers and focal adhesions in 3T3 fibroblasts,” The Journal of Cell Biology, vol. 150, no. 4, pp. 797–806, 2000. View at Publisher · View at Google Scholar · View at Scopus
  53. M. Chrzanowska-Wodnicka and K. Burridge, “Rho-stimulated contractility drives the formation of stress fibers and focal adhesions,” Journal of Cell Biology, vol. 133, no. 6, pp. 1403–1415, 1996. View at Publisher · View at Google Scholar · View at Scopus
  54. E. Sahai and C. J. Marshall, “ROCK and Dia have opposing effects on adherens junctions downstream of Rho,” Nature Cell Biology, vol. 4, no. 6, pp. 408–415, 2002. View at Publisher · View at Google Scholar · View at Scopus
  55. A. I. Ivanov, S. N. Samarin, M. Bachar, C. A. Parkos, and A. Nusrat, “Protein kinase C activation disrupts epithelial apical junctions via ROCK-II dependent stimulation of actomyosin contractility,” BMC Cell Biology, vol. 10, article 36, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. S. N. Samarin, A. I. Ivanov, G. Flatau, C. A. Parkos, and A. Nusrat, “Rho/Rho-associated kinase-II signaling mediates disassembly of epithelial apical junctions,” Molecular Biology of the Cell, vol. 18, no. 9, pp. 3429–3439, 2007. View at Publisher · View at Google Scholar · View at Scopus
  57. J. A. G. McKenzie and A. J. Ridley, “Roles of Rho/ROCK and MLCK in TNF-α-induced changes in endothelial morphology and permeability,” Journal of Cellular Physiology, vol. 213, no. 1, pp. 221–228, 2007. View at Publisher · View at Google Scholar · View at Scopus
  58. K. Zhang, H. Zhang, H. Xiang et al., “TGF-β1 induces the dissolution of tight junctions in human renal proximal tubular cells: role of the RhoA/ROCK signaling pathway,” International Journal of Molecular Medicine, vol. 32, no. 2, pp. 464–468, 2013. View at Publisher · View at Google Scholar · View at Scopus
  59. L.-L. Wu, W.-H. Peng, W.-T. Kuo et al., “Commensal bacterial endocytosis in epithelial cells is dependent on myosin light chain kinase-activated brush border fanning by interferon-γ,” The American Journal of Pathology, vol. 184, no. 8, pp. 2260–2274, 2014. View at Publisher · View at Google Scholar · View at Scopus
  60. T. Y. Ma, M. A. Boivin, D. Ye, A. Pedram, and H. M. Said, “Mechanism of TNF-α modulation of Caco-2 intestinal epithelial tight junction barrier: role of myosin light-chain kinase protein expression,” American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 288, no. 3, pp. G422–G430, 2005. View at Publisher · View at Google Scholar · View at Scopus
  61. K. E. Thomas, A. Sapone, A. Fasano, and S. N. Vogel, “Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in Celiac disease,” The Journal of Immunology, vol. 176, no. 4, pp. 2512–2521, 2006. View at Publisher · View at Google Scholar · View at Scopus
  62. D. Ye, I. Ma, and T. Y. Ma, “Molecular mechanism of tumor necrosis factor-α modulation of intestinal epithelial tight junction barrier,” American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 290, no. 3, pp. G496–G504, 2006. View at Publisher · View at Google Scholar · View at Scopus
  63. A. I. Ivanov, C. A. Parkos, and A. Nusrat, “Cytoskeletal regulation of epithelial barrier function during inflammation,” The American Journal of Pathology, vol. 177, no. 2, pp. 512–524, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. M. Bruewer, A. Luegering, T. Kucharzik et al., “Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms,” The Journal of Immunology, vol. 171, no. 11, pp. 6164–6172, 2003. View at Publisher · View at Google Scholar · View at Scopus
  65. P. Suenaert, V. Bulteel, L. Lemmens et al., “Anti-tumor necrosis factor treatment restores the gut barrier in Crohn's disease,” The American Journal of Gastroenterology, vol. 97, no. 8, pp. 2000–2004, 2002. View at Publisher · View at Google Scholar · View at Scopus
  66. G. Järnerot, E. Hertervig, I. Friis-Liby et al., “Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study,” Gastroenterology, vol. 128, no. 7, pp. 1805–1811, 2005. View at Publisher · View at Google Scholar · View at Scopus
  67. M. Niessner and B. A. Volk, “Altered Th1/Th2 cytokine profiles in the intestinal mucosa of patients with inflammatory bowel disease as assessed by quantitative reversed transcribed polymerase chain reaction (RT-PCR),” Clinical and Experimental Immunology, vol. 101, no. 3, pp. 428–435, 1995. View at Google Scholar · View at Scopus
  68. L. Haep, N. Britzen-Laurent, T. G. Weber et al., “Interferon gamma counteracts the angiogenic switch and induces vascular permeability in dextran sulfate sodium colitis in mice,” Inflammatory Bowel Diseases, vol. 21, no. 10, pp. 2360–2371, 2015. View at Publisher · View at Google Scholar · View at Scopus
  69. R. Rismo, T. Olsen, G. Cui, I. Christiansen, J. Florholmen, and R. Goll, “Mucosal cytokine gene expression profiles as biomarkers of response to infliximab in ulcerative colitis,” Scandinavian Journal of Gastroenterology, vol. 47, no. 5, pp. 538–547, 2012. View at Publisher · View at Google Scholar · View at Scopus
  70. Q. L. Liu, L. Huang, Q. J. Zhao, Q. Li, and Z. He, “Relationship between serum interleukin-17 level and inflammatory bowel disease,” Journal of Biological Regulators and Homeostatic Agents, vol. 30, no. 1, pp. 181–188, 2016. View at Google Scholar
  71. D. E. Winchester and C. J. Pepine, “Angina treatments and prevention of cardiac events: an appraisal of the evidence,” European Heart Journal Supplements, vol. 17, pp. G10–G18, 2015. View at Publisher · View at Google Scholar
  72. M. L. Rodríguez-Perlvárez, V. García-Sánchez, C. M. Villar-Pastor et al., “Role of serum cytokine profile in ulcerative colitis assessment,” Inflammatory Bowel Diseases, vol. 18, no. 10, pp. 1864–1871, 2012. View at Publisher · View at Google Scholar · View at Scopus
  73. D. Zaidi, M. Bording-Jorgensen, H. Q. Huynh et al., “Increased epithelial gap density in the non-inflamed duodenum of children with inflammatory bowel diseases,” Journal of Pediatric Gastroenterology and Nutrition, 2016. View at Publisher · View at Google Scholar
  74. F. Koning, “Celiac disease: caught between a rock and a hard place,” Gastroenterology, vol. 129, no. 4, pp. 1294–1301, 2005. View at Publisher · View at Google Scholar · View at Scopus
  75. D. Schuppan, Y. Junker, and D. Barisani, “Celiac disease: from pathogenesis to novel therapies,” Gastroenterology, vol. 137, no. 6, pp. 1912–1933, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. M. R. Barbaro, A. Di Sabatino, C. Cremon et al., “Interferon-γ is increased in the gut of patients with irritable bowel syndrome and modulates serotonin metabolism,” American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 310, no. 6, pp. G439–G447, 2016. View at Publisher · View at Google Scholar
  77. J. Chen, Y. Zhang, and Z. Deng, “Imbalanced shift of cytokine expression between T helper 1 and T helper 2 (Th1/Th2) in intestinal mucosa of patients with post-infectious irritable bowel syndrome,” BMC Gastroenterology, vol. 12, article 91, 2012. View at Publisher · View at Google Scholar · View at Scopus
  78. M. Vivinus-Nébot, G. Frin-Mathy, H. Bzioueche et al., “Functional bowel symptoms in quiescent inflammatory bowel diseases: role of epithelial barrier disruption and low-grade inflammation,” Gut, vol. 63, no. 5, pp. 744–752, 2014. View at Publisher · View at Google Scholar · View at Scopus
  79. S. Seyedmirzaee, M. M. Hayatbakhsh, B. Ahmadi et al., “Serum immune biomarkers in irritable bowel syndrome,” Clinics and Research in Hepatology and Gastroenterology, 2016. View at Publisher · View at Google Scholar · View at Scopus
  80. B. L. Pike, K. A. Paden, A. N. Alcala et al., “Immunological biomarkers in postinfectious irritable bowel syndrome,” Journal of Travel Medicine, vol. 22, no. 4, pp. 242–250, 2015. View at Publisher · View at Google Scholar · View at Scopus
  81. T. Liebregts, B. Adam, C. Bredack et al., “Small bowel homing T cells are associated with symptoms and delayed gastric emptying in functional dyspepsia,” The American Journal of Gastroenterology, vol. 106, no. 6, pp. 1089–1098, 2011. View at Publisher · View at Google Scholar · View at Scopus
  82. J.-P. Segain, D. R. de la Blétière, V. Sauzeau et al., “Rho kinase blockade prevents inflammation via nuclear factor κB inhibition: evidence in Crohn's disease and experimental colitis,” Gastroenterology, vol. 124, no. 5, pp. 1180–1187, 2003. View at Publisher · View at Google Scholar · View at Scopus
  83. A. J. Monsuur, P. I. W. de Bakker, B. Z. Alizadeh et al., “Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect,” Nature Genetics, vol. 37, no. 12, pp. 1341–1344, 2005. View at Publisher · View at Google Scholar · View at Scopus
  84. K. Gecse, R. Róka, L. Ferrier et al., “Increased faecal serine protease activity in diarrhoeic IBS patients: a colonic lumenal factor impairing colonic permeability and sensitivity,” Gut, vol. 57, no. 5, pp. 591–599, 2008. View at Publisher · View at Google Scholar · View at Scopus
  85. A. Kaser, S. Zeissig, and R. S. Blumberg, “Inflammatory bowel disease,” Annual Review of Immunology, vol. 28, pp. 573–621, 2010. View at Publisher · View at Google Scholar · View at Scopus
  86. K. J. Maloy and F. Powrie, “Intestinal homeostasis and its breakdown in inflammatory bowel disease,” Nature, vol. 474, no. 7351, pp. 298–306, 2011. View at Publisher · View at Google Scholar · View at Scopus
  87. P. Munkholm, E. Langholz, D. Hollander et al., “Intestinal permeability in patients with Crohn's disease and ulcerative colitis and their first degree relatives,” Gut, vol. 35, no. 1, pp. 68–72, 1994. View at Publisher · View at Google Scholar · View at Scopus
  88. Y. Huang, S. Xiao, and Q. Jiang, “Role of Rho kinase signal pathway in inflammatory bowel disease,” International Journal of Clinical and Experimental Medicine, vol. 8, no. 3, pp. 3089–3097, 2015. View at Google Scholar · View at Scopus
  89. G. Toedter, K. Li, S. Sague et al., “Genes associated with intestinal permeability in ulcerative colitis: changes in expression following infliximab therapy,” Inflammatory Bowel Diseases, vol. 18, no. 8, pp. 1399–1410, 2012. View at Publisher · View at Google Scholar · View at Scopus
  90. A. M. Muise, T. D. Walters, W. K. Glowacka et al., “Polymorphisms in E-cadherin (CDH1) result in a mislocalised cytoplasmic protein that is associated with Crohn's disease,” Gut, vol. 58, no. 8, pp. 1121–1127, 2009. View at Publisher · View at Google Scholar · View at Scopus
  91. N. Gassler, C. Rohr, A. Schneider et al., “Inflammatory bowel disease is associated with changes of enterocytic junctions,” American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 281, no. 1, pp. G216–G228, 2001. View at Google Scholar · View at Scopus
  92. T. Suzuki, “Regulation of intestinal epithelial permeability by tight junctions,” Cellular and Molecular Life Sciences, vol. 70, no. 4, pp. 631–659, 2013. View at Publisher · View at Google Scholar · View at Scopus
  93. R. Al-Sadi, S. Guo, D. Ye et al., “Mechanism of IL-1β modulation of intestinal epithelial barrier involves p38 kinase and activating transcription factor-2 activation,” Journal of Immunology, vol. 190, no. 12, pp. 6596–6606, 2013. View at Publisher · View at Google Scholar · View at Scopus
  94. J. Y. Kang, A. H. Y. Kang, A. Green, K. A. Gwee, and K. Y. Ho, “Systematic review: worldwide variation in the frequency of coeliac disease and changes over time,” Alimentary Pharmacology and Therapeutics, vol. 38, no. 3, pp. 226–245, 2013. View at Publisher · View at Google Scholar · View at Scopus
  95. G. R. Sander, A. G. Cummins, T. Henshall, and B. C. Powell, “Rapid disruption of intestinal barrier function by gliadin involves altered expression of apical junctional proteins,” FEBS Letters, vol. 579, no. 21, pp. 4851–4855, 2005. View at Google Scholar
  96. P. Goswami, P. Das, A. K. Verma et al., “Are alterations of tight junctions at molecular and ultrastructural level different in duodenal biopsies of patients with celiac disease and Crohn's disease?” Virchows Archiv, vol. 465, no. 5, pp. 521–530, 2014. View at Publisher · View at Google Scholar · View at Scopus
  97. A. Jauregi-Miguel, N. Fernandez-Jimenez, I. Irastorza, L. Plaza-Izurieta, J. C. Vitoria, and J. R. Bilbao, “Alteration of tight junction gene expression in celiac disease,” Journal of Pediatric Gastroenterology and Nutrition, vol. 58, no. 6, pp. 762–767, 2014. View at Publisher · View at Google Scholar · View at Scopus
  98. L. Tuckova, J. Novotna, P. Novak et al., “Activation of macrophages by gliadin fragments: isolation and characterization of active peptide,” Journal of Leukocyte Biology, vol. 71, no. 4, pp. 625–631, 2002. View at Google Scholar
  99. S. Helms, “Celiac disease and gluten-associated diseases,” Alternative Medicine Review, vol. 10, no. 3, pp. 172–192, 2005. View at Google Scholar · View at Scopus
  100. G. F. Longstreth, W. G. Thompson, W. D. Chey, L. A. Houghton, F. Mearin, and R. C. Spiller, “Functional bowel disorders,” Gastroenterology, vol. 130, no. 5, pp. 1480–1491, 2006. View at Publisher · View at Google Scholar · View at Scopus
  101. M. Rajilić-Stojanović, E. Biagi, H. G. H. J. Heilig et al., “Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome,” Gastroenterology, vol. 141, no. 5, pp. 1792–1801, 2011. View at Publisher · View at Google Scholar · View at Scopus
  102. J.-F. Turcotte, D. Kao, S. J. Mah et al., “Breaks in the wall: increased gaps in the intestinal epithelium of irritable bowel syndrome patients identified by confocal laser endomicroscopy (with videos),” Gastrointestinal Endoscopy, vol. 77, no. 4, pp. 624–630, 2013. View at Publisher · View at Google Scholar · View at Scopus
  103. N. Bertiaux-Vandaële, S. B. Youmba, L. Belmonte et al., “The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype,” The American Journal of Gastroenterology, vol. 106, no. 12, pp. 2165–2173, 2011. View at Publisher · View at Google Scholar · View at Scopus
  104. M. Bashashati, N. Rezaei, C. N. Andrews et al., “Cytokines and irritable bowel syndrome: where do we stand?” Cytokine, vol. 57, no. 2, pp. 201–209, 2012. View at Publisher · View at Google Scholar · View at Scopus
  105. J. Matricon, M. Meleine, A. Gelot et al., “Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome,” Alimentary Pharmacology & Therapeutics, vol. 36, no. 11-12, pp. 1009–1031, 2012. View at Publisher · View at Google Scholar
  106. H. Lee, J. H. Park, D. I. Park et al., “Mucosal mast cell count is associated with intestinal permeability in patients with diarrhea predominant irritable bowel syndrome,” Journal of Neurogastroenterology and Motility, vol. 19, no. 2, pp. 244–250, 2013. View at Publisher · View at Google Scholar · View at Scopus
  107. Y.-J. Hu, Y.-D. Wang, F.-Q. Tan, and W.-X. Yang, “Regulation of paracellular permeability: factors and mechanisms,” Molecular Biology Reports, vol. 40, no. 11, pp. 6123–6142, 2013. View at Publisher · View at Google Scholar · View at Scopus
  108. A. Ait-Belgnaoui, S. Bradesi, J. Fioramonti, V. Theodorou, and L. Bueno, “Acute stress-induced hypersensitivity to colonic distension depends upon increase in paracellular permeability: role of myosin light chain kinase,” Pain, vol. 113, no. 1-2, pp. 141–147, 2005. View at Publisher · View at Google Scholar · View at Scopus
  109. D. R. Clayburgh, T. A. Barrett, Y. Tang et al., “Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo,” Journal of Clinical Investigation, vol. 115, no. 10, pp. 2702–2715, 2005. View at Publisher · View at Google Scholar · View at Scopus
  110. A. C. Ford, A. Marwaha, R. Sood, and P. Moayyedi, “Global prevalence of, and risk factors for, uninvestigated dyspepsia: a meta-analysis,” Gut, vol. 64, pp. 1049–1057, 2015. View at Publisher · View at Google Scholar · View at Scopus
  111. S. Kindt, A. Tertychnyy, G. De Hertogh, K. Geboes, and J. Tack, “Intestinal immune activation in presumed post-infectious functional dyspepsia,” Neurogastroenterology and Motility, vol. 21, no. 8, pp. 832–e56, 2009. View at Publisher · View at Google Scholar · View at Scopus
  112. S. Futagami, T. Shindo, T. Kawagoe et al., “Migration of eosinophils and CCR2-/CD68-double positive cells into the duodenal mucosa of patients with postinfectious functional dyspepsia,” The American Journal of Gastroenterology, vol. 105, no. 8, pp. 1835–1842, 2010. View at Publisher · View at Google Scholar · View at Scopus
  113. J. Mankertz and J.-D. Schulzke, “Altered permeability in inflammatory bowel disease: pathophysiology and clinical implications,” Current Opinion in Gastroenterology, vol. 23, no. 4, pp. 379–383, 2007. View at Publisher · View at Google Scholar · View at Scopus
  114. Z. Mujagic, S. Ludidi, D. Keszthelyi et al., “Small intestinal permeability is increased in diarrhoea predominant IBS, while alterations in gastroduodenal permeability in all IBS subtypes are largely attributable to confounders,” Alimentary Pharmacology & Therapeutics, vol. 40, no. 3, pp. 288–297, 2014. View at Publisher · View at Google Scholar · View at Scopus
  115. M. Takamura, M. Sakamoto, T. Genda, T. Ichida, H. Asakura, and S. Hirohashi, “Inhibition of intrahepatic metastasis of human hepatocellular carcinoma by Rho-associated protein kinase inhibitor Y-27632,” Hepatology, vol. 33, no. 3, pp. 577–581, 2001. View at Publisher · View at Google Scholar · View at Scopus
  116. M. S. Wainwright, J. Rossi, J. Schavocky et al., “Protein kinase involved in lung injury susceptibility: evidence from enzyme isoform genetic knockout and in vivo inhibitor treatment,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 10, pp. 6233–6238, 2003. View at Publisher · View at Google Scholar · View at Scopus
  117. R. Reynoso, R. M. Perrin, J. W. Breslin et al., “A role for long chain myosin light chain kinase (MLCK-210) in microvascular hyperpermeability during severe burns,” Shock, vol. 28, no. 5, pp. 589–595, 2007. View at Publisher · View at Google Scholar · View at Scopus