The Role of the Epithelial Barrier in Inflammatory Bowel Disease

  • Edward E. S. Nieuwenhuis
  • Richard S. Blumberg
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 579)

Conclusion

The epithelial barrier protects the intestine from harmful antigens. The intestinal epithelial cell produces a wide array of molecules that play a role in initiating, maintaining, but also preventing and controlling mucosal inflammation. A defect in epithelial cell regulated barrier function may lead to continued exposure of intestinal immune cells to bacterially derived molecules leading to destructive intestinal inflammation that characterizes IBD.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002; 347(6):417–29.PubMedCrossRefGoogle Scholar
  2. 2.
    Sartor RB. Innate immunity in the pathogenesis and therapy of IBD. J Gastroenterol 2003; 38(Suppl 15):43–7.PubMedGoogle Scholar
  3. 3.
    Ogura Y, Bonen DK, Inohara N et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 2001; 411(6837):603–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Hugot JP, Chamaillard M, Zouali H et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 2001; 411(6837):599–603.PubMedCrossRefGoogle Scholar
  5. 5.
    Cario E, Podolsky DK. Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 2000; 68(12):7010–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Blumberg RS, Saubermann LJ, Strober W. Animal models of mucosal inflammation and their relation to human inflammatory bowel disease. Curr Opin Immunol 1999; 11(6):648–56.PubMedCrossRefGoogle Scholar
  7. 7.
    Swidsinski A, Ladhoff A, Pernthaler A et al. Mucosal flora in inflammatory bowel disease. Gastroenterology 2002; 122(1):44–54.PubMedCrossRefGoogle Scholar
  8. 8.
    Montgomery SM, Morris DL, Pounder RE et al. Paramyxovirus infections in childhood and subsequent inflammatory bowel disease. Gastroenterology 1999; 116(4):796–803.PubMedCrossRefGoogle Scholar
  9. 9.
    Greenstein RJ. Is Crohn’s disease caused by a mycobacterium? Comparisons with leprosy, tuberculosis, and Johne’s disease. Lancet Infect Dis 2003; 3(8):507–14.PubMedCrossRefGoogle Scholar
  10. 10.
    Liu Y, van Kruiningen HJ, West AB et al. Immunocytochemical evidence of Listeria, Escherichia coli, and Streptococcus antigens in Crohn’s disease. Gastroenterology 1995; 108(5):1396–404.PubMedCrossRefGoogle Scholar
  11. 11.
    Podolsky DK. The future of IBD treatment. J Gastroenterol 2003; 38(Suppl 15):63–6.PubMedGoogle Scholar
  12. 12.
    Colombel JF, Cortot A, van Kruiningen HJ. Antibiotics in Crohn’s disease. Gut 2001; 48(5):647.PubMedCrossRefGoogle Scholar
  13. 13.
    Mimura T, Rizzello F, Helwig U et al. Four-week open-label trial of metronidazole and ciprofloxacin for the treatment of recurrent or refractory pouchitis. Aliment Pharmacol Ther 2002; 16(5):909–17.PubMedCrossRefGoogle Scholar
  14. 14.
    Madsen KL. Inflammatory bowel disease: Lessons from the IL-10 gene-deficient mouse. Clin Invest Med 2001; 24(5):250–7.PubMedGoogle Scholar
  15. 15.
    Waidmann M, Bechtold O, Frick JS et al. Bacteroides vulgatus protects against Escherichia coli-induced colitis in gnotobiotic interleukin-2-deficient mice. Gastroenterology 2003; 125(1):162–77.PubMedCrossRefGoogle Scholar
  16. 16.
    Madsen KL, Malfair D, Gray D et al. Interleukin-10 gene-deficient mice develop a primary intestinal permeability defect in response to enteric microflora. Inflamm Bowel Dis 1999; 5(4):262–70.PubMedCrossRefGoogle Scholar
  17. 17.
    Gionchetti P, Rizzello F, Venturi A et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: A double-blind, placebo-controlled trial. Gastroenterology 2000; 119(2):305–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Rembacken BJ, Snelling AM, Hawkey PM et al. Nonpathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: A randomised trial. Lancet 1999; 354(9179):635–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Haller D, Russo MP, Sartor RB et al. IKK beta and phosphatidylinositol 3-kinase/Akt participate in nonpathogenic Gram-negative enteric bacteria-induced RelA phosphorylation and NF-kappa B activation in both primary and intestinal epithelial cell lines. J Biol Chem 2002; 277(41):38168–78.PubMedCrossRefGoogle Scholar
  20. 20.
    Cario E, Rosenberg IM, Brandwein SL et al. Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing Toll-like receptors. J Immunol 2000; 164(2):966–72.PubMedGoogle Scholar
  21. 21.
    Inohara N, Ogura Y, Fontalba A et al. Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn’s disease. J Biol Chem 2003; 278(8):5509–12.PubMedCrossRefGoogle Scholar
  22. 22.
    Lala S, Ogura Y, Osborne C et al. Crohn’s disease and the NOD2 gene: A role for paneth cells. Gastroenterology 2003; 125(1):47–57.PubMedCrossRefGoogle Scholar
  23. 23.
    Rosenstiel P, Fantini M, Brautigam K et al. TNF-alpha and IFN-gamma regulate the expression of the NOD2 (CARD15) gene in human intestinal epithelial cells. Gastroenterology 2003; 124(4):1001–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Gutierrez O, Pipaon C, Inohara N et al. Induction of Nod2 in myelomonocytic and intestinal epithelial cells via nuclear factor-kappa B activation. J Biol Chem 2002; 277(44):41701–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Z’Graggen K, Walz A, Mazzucchelli L et al. The C-X-C chemokine ENA-78 is preferentially expressed in intestinal epithelium in inflammatory bowel disease. Gastroenterology 1997; 113(3):808–16.PubMedCrossRefGoogle Scholar
  26. 26.
    Banks C, Bateman A, Payne R et al. Chemokine expression in IBD. Mucosal chemokine expression is unselectively increased in both ulcerative colitis and Crohn’s disease. J Pathol 2003; 199(1):28–35.PubMedCrossRefGoogle Scholar
  27. 27.
    Reinecker HC, Loh EY, Ringler DJ et al. Monocyte-chemoattractant protein 1 gene expression in intestinal epithelial cells and inflammatory bowel disease mucosa. Gastroenterology 1995; 108(1):40–50.PubMedCrossRefGoogle Scholar
  28. 28.
    Vainer B, Sorensen S, Nielsen OH et al. Subcellular localization of intercellular adhesion molecule-1 in colonic mucosa in ulcerative colitis. Ultrastruct Pathol 2002; 26(2):113–21.PubMedCrossRefGoogle Scholar
  29. 29.
    Dwinell MB, Lugering N, Eckmann L et al. Regulated production of interferon-inducible T-cell chemoattractants by human intestinal epithelial cells. Gastroenterology 2001; 120(1):49–59.PubMedCrossRefGoogle Scholar
  30. 30.
    Kwon JH, Keates S, Bassani L et al. Colonic epithelial cells are a major site of macrophage inflammatory protein 3alpha (MIP-3alpha) production in normal colon and inflammatory bowel disease. Gut 2002; 51(6):818–26.PubMedCrossRefGoogle Scholar
  31. 31.
    Fuss IJ, Neurath M, Boirivant M et al. Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn’s disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol 1996; 157(3):1261–70.PubMedGoogle Scholar
  32. 32.
    Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol 2003; 3(7):521–33.PubMedCrossRefGoogle Scholar
  33. 33.
    Eckmann L, Jung HC, Schurer-Maly C et al. Differential cytokine expression by human intestinal epithelial cell lines: Regulated expression of interleukin 8. Gastroenterology 1993; 105(6):1689–97.PubMedGoogle Scholar
  34. 34.
    Taylor CT, Dzus AL, Colgan SP. Autocrine regulation of epithelial permeability by hypoxia: Role for polarized release of tumor necrosis factor alpha. Gastroenterology 1998; 114(4):657–68.PubMedCrossRefGoogle Scholar
  35. 35.
    Ishiguro Y. Mucosal proinflammatory cytokine production correlates with endoscopic activity of ulcerative colitis. J Gastroenterol 1999; 34(1):66–74.PubMedCrossRefGoogle Scholar
  36. 36.
    ering N, Kucharzik T, Gockel H et al. Human intestinal epithelial cells down-regulate IL-8 expression in human intestinal microvascular endothelial cells; Role of transforming growth factor-beta 1 (TGF-beta1). Clin Exp Immunol 1998; 114(3):377–84.CrossRefGoogle Scholar
  37. 37.
    Autschbach F, Braunstein J, Helmke B et al. In situ expression of interleukin-10 in noninflamed human gut and in inflammatory bowel disease. Am J Pathol 1998; 153(1):121–30.PubMedCrossRefGoogle Scholar
  38. 38.
    Colgan SP, Hershberg RM, Furuta GT et al. Ligation of intestinal epithelial CD1d induces bioactive IL-10: Critical role of the cytoplasmic tail in autocrine signaling. Proc Natl Acad Sci USA 1999; 96(24):13938–43.PubMedCrossRefGoogle Scholar
  39. 39.
    van Dullemen HM, van Deventer SJ, Hommes DW et al. Treatment of Crohn’s disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology 1995; 109(1):129–35.PubMedCrossRefGoogle Scholar
  40. 40.
    Einerhand AW, Renes IB, Makkink MK et al. Role of mucins in inflammatory bowel disease: Important lessons from experimental models. Eur J Gastroenterol Hepatol 2002; 14(7):757–65.PubMedCrossRefGoogle Scholar
  41. 41.
    Buisine MP, Desreumaux P, Leteurtre E et al. Mucin gene expression in intestinal epithelial cells in Crohn’s disease. Gut 2001; 49(4):544–51.PubMedCrossRefGoogle Scholar
  42. 42.
    Wehkamp J, Schwind B, Herrlinger KR et al. Innate immunity and colonic inflammation: Enhanced expression of epithelial alpha-defensins. Dig Dis Sci 2002; 47(6):1349–55.PubMedCrossRefGoogle Scholar
  43. 43.
    Wehkamp J, Fellermann K, Herrlinger KR et al. Human beta-defensin 2 but not beta-defensin 1 is expressed preferentially in colonic mucosa of inflammatory bowel disease. Eur J Gastroenterol Hepatol 2002; 14(7):745–52.PubMedCrossRefGoogle Scholar
  44. 44.
    Fahlgren A, Hammarstrom S, Danielsson A et al. Increased expression of antimicrobial peptides and lysozyme in colonic epithelial cells of patients with ulcerative colitis. Clin Exp Immunol 2003; 131(1):90–101.PubMedCrossRefGoogle Scholar
  45. 45.
    Hooper LV, Stappenbeck TS, Hong CV et al. Angiogenins: A new class of microbicidal proteins involved in innate immunity. Nat Immunol 2003; 4(3):269–73.PubMedCrossRefGoogle Scholar
  46. 46.
    Rescigno M, Urbano M, Valzasina B et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2001; 2(4):361–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Dickinson BL, Badizadegan K, Wu Z et al. Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line. J Clin Invest 1999; 104(7):903–11.PubMedCrossRefGoogle Scholar
  48. 48.
    van de Wal Y, Corazza N, Allez M et al. Delineation of a CD1d-restricted antigen presentation pathway associated with human and mouse intestinal epithelial cells. Gastroenterology 2003; 124(5):1420–31.PubMedCrossRefGoogle Scholar
  49. 49.
    Hershberg RM, Mayer LF. Antigen processing and presentation by intestinal epithelial cells — polarity and complexity. Immunol Today 2000; 21(3):123–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Heller F, Fuss IJ, Nieuwenhuis EE et al. Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. Immunity 2002; 17(5):629–38.PubMedCrossRefGoogle Scholar
  51. 51.
    MacDonald TT, Spencer J. Evidence that activated mucosal T cells play a role in the pathogenesis of enteropathy in human small intestine. J Exp Med 1988; 167(4):1341–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Telega GW, Baumgart DC, Carding SR. Uptake and presentation of antigen to T cells by primary colonic epithelial cells in normal and diseased states. Gastroenterology 2000; 119(6):1548–59.PubMedCrossRefGoogle Scholar
  53. 53.
    Roediger WE, Duncan A, Kapaniris O et al. Reducing sulfur compounds of the colon impair colonocyte nutrition: Implications for ulcerative colitis. Gastroenterology 1993; 104(3):802–9.PubMedGoogle Scholar
  54. 54.
    Mashimo H, Wu DC, Podolsky DK et al. Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor. Science 1996; 274(5285):262–5.PubMedCrossRefGoogle Scholar
  55. 55.
    Klein W, Tromm A, Griga T et al. A polymorphism in the IL11 gene is associated with ulcerative colitis. Genes Immun 2002; 3(8):494–6.PubMedCrossRefGoogle Scholar
  56. 56.
    Vainer B, Nielsen OH, Horn T. Expression of E-selectin, sialyl Lewis X, and macrophage inflammatory protein-1alpha by colonic epithelial cells in ulcerative colitis. Dig Dis Sci 1998; 43(3):596–608.PubMedCrossRefGoogle Scholar
  57. 57.
    Jung HC, Eckmann L, Yang SK et al. A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J Clin Invest 1995; 95(1):55–65.PubMedCrossRefGoogle Scholar
  58. 58.
    McGee DW, Bamberg T, Vitkus SJ et al. A synergistic relationship between TNF-alpha, IL-1 beta, and TGF-beta 1 on IL-6 secretion by the IEC-6 intestinal epithelial cell line. Immunology 1995; 86(1):6–11.PubMedGoogle Scholar
  59. 59.
    Casola A, Estes MK, Crawford SE et al. Rotavirus infection of cultured intestinal epithelial cells induces secretion of CXC and CC chemokines. Gastroenterology 1998; 114(5):947–55.PubMedCrossRefGoogle Scholar
  60. 60.
    Schuerer-Maly CC, Eckmann L, Kagnoff MF et al. Colonic epithelial cell lines as a source of interleukin-8: Stimulation by inflammatory cytokines and bacterial lipopolysaccharide. Immunology 1994; 81(1):85–91.PubMedGoogle Scholar

Copyright information

© Eurekah.com and Springer Science+Business Media 2006

Authors and Affiliations

  • Edward E. S. Nieuwenhuis
    • 1
  • Richard S. Blumberg
    • 2
  1. 1.Laboratory of Pediatrics, Department of Pediatric GastroenterologyErasmus MCRotterdamThe Netherlands
  2. 2.Gastroenterology Division and Laboratory of Mucosal ImmunologyBrigham and Women’s HospitalHarvardUSA

Personalised recommendations