Barrier dysfunction due to distinct defensin deficiencies in small intestinal and colonic crohn’ s disease

Mucosal Immunology

Volumn 1, Issue , 2008, Pages 67-74

  Wehkamp, J ^a   Koslowski, M ^b   Wang, G ^b   Stange, E F ^a  

^a ROBERT BOSCH HOSPITAL   (Germany)

^b UNIVERSITY OF TÜBINGEN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BETA DEFENSIN; CASPASE RECRUITMENT DOMAIN PROTEIN 15; DEFENSIN; MESALAZINE; PLACEBO; PROBIOTIC AGENT; WNT PROTEIN; ZINC;

ANTIMICROBIAL ACTIVITY; BACTERICIDAL ACTIVITY; CELL DIFFERENTIATION; CHRONIC INFLAMMATION; CLINICAL TRIAL; CROHN DISEASE; ESCHERICHIA COLI; FRAMESHIFT MUTATION; GASTROINTESTINAL INFECTION; GRAFT REJECTION; GRAFT VERSUS HOST REACTION; HUMAN; INNATE IMMUNITY; INTESTINE TRANSPLANTATION; LACTOBACILLUS; NONHUMAN; PANETH CELL; PERMEABILITY BARRIER; PRIORITY JOURNAL; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; SMALL INTESTINE MUCOSA; ULCERATIVE COLITIS; ZINC DEFICIENCY;

ANIMALS; ANTI-BACTERIAL AGENTS; DEFENSINS; GENE DOSAGE; GRAFT VS HOST DISEASE; HUMANS; INTESTINAL DISEASES; SIGNAL TRANSDUCTION;

EID: 54349102824     PISSN: 19330219     EISSN: 19353456     Source Type: Journal    
DOI: 10.1038/mi.2008.48     Document Type: Review

References (58)

1. Zasloff, M. Antimicrobial peptides of multicellular organisms. Nature 415, 389-395 (2002).
2. Dommett, R., Zilbauer, M., George, J. T. & Bajaj-Elliott, M. Innate immune defence in the human gastrointestinal tract. Mol. Immunol. 42, 903-912 (2005).
3. Bevins, C. L. The Paneth cell and the innate immune response. Curr. Opin. Gastroenterol. 20, 572-580 (2004).
4. Wehkamp, J., Fellermann, K., Herrlinger, K., Bevins, C. & Stange, E. F. Mechanisms of disease: defensins in gastrointestinal diseases. Nat. Clin Pract.: Gastroenterol. Hepatol. 2, 406-415 (2005).
5. Wehkamp, J., Schmid, M. & Stange, E. F. Defensins and other antimicrobial peptides in inflammatory bowel disease. Curr. Opin. Gastroenterol. 23, 370-378 (2007).
6. Boman, H. G. Peptide antibiotics and their role in innate immunity. Annu. Rev. Immunol. 13, 61-92 (1995).
7. Sallenave, J. M. Antimicrobial activity of antiproteinases. Biochem. Soc. Trans. 30, 111-115 (2002).
8. Hiemstra, P. S. Novel roles of protease inhibitors in infection and inflammation. Biochem. Soc. Trans. 30, 116-120 (2002).
9. Canny, G. et al. Functional and biochemical characterization of epithelial bactericidal/permeability-increasing protein. Am. J. Physiol. Gastrointest. Liver Physiol. 290, G557-G567 (2006).
10. Canny, G. et al. Lipid mediator-induced expression of bactericidal/permeability-increasing protein (BPI) in human mucosal epithelia. Proc. Natl. Acad. Sci. USA 99, 3902-3907 (2002).
11. Simon, G. L. & Gorbach, S. L. Normal alimentary tract microflora. In Infections of the Gastrointestinal Tract (Blaser, M.J., Smith, P.D., Ravdin, H.B., Greenberg, R.L. & Guerrant, R.L., eds) 53-69 (Raven Press, New York, 1995).
12. McCracken, V. J. & Lorenz, R. G. The gastrointestinal ecosystem: a precarious alliance among epithelium, immunity and microbiota. Microreview. Cell. Microbiol. 3, 1-11 (2001).
13. Zhao, C., Wang, I. & Lehrer, R. I. Widespread expression of beta-defensin hBD-1 in human secretory glands and epithelial cells. FEBS Lett. 396, 319-322 (1996).
14. O ’ Neil, D. A. et al. Expression and regulation of the human β-defensins hBD-1 and hBD-2 in intestinal epithelium. J. Immunol. 163, 6718-6724 (1999).
15. Cunliffe, R. N. et al. Human defensin 5 is stored in precursor form in normal Paneth cells and is expressed by some villous epithelial cells and by metaplastic Paneth cells in the colon in inflammatory bowel disease. Gut 48, 176-185 (2001).
16. Wehkamp, J. et al. Defensin pattern in chronic gastritis: HBD-2 is differentially expressed with respect to Helicobacter pylori status. J. Clin. Pathol. 56, 352-357 (2003).
17. Shen, B. et al. Human defensin 5 expression in intestinal metaplasia of the upper gastrointestinal tract. J. Clin. Pathol. 58, 687-694 (2005).
18. Wehkamp, J. et al. Paneth cell antimicrobial peptides: topographical distribution and quantification in human gastrointestinal tissues. FEBS Lett. 580, 5344-5350 (2006).
19. Wehkamp, J. et al. Reduced Paneth cell alpha-defensins in ileal Crohn’s disease. PNAS 102, 18129-18134 (2005).
20. Porter, E. M., Bevins, C. L., Ghosh, D. & Ganz, T. The multifaceted Paneth cell. Cell Mol. Life Sci. 59, 156-170 (2002).
21. Salzman, N. H., Ghosh, D., Huttner, K. M., Paterson, Y. & Bevins, C. L. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 422, 522-526 (2003).
22. Ayabe, T. et al. Secretion of microbicidal alpha-defensins by intestinal Paneth cell response to bacteria. Nat. Immunol. 1, 113-118 (2000).
23. Inohara, N., Chamaillard, M., McDonald, C. & Nunez, G. NOD-LRR proteins: role in host-microbial interactions and inflammatory disease. Annu. Rev. Biochem. 19, 355-383 (2005).
24. Podolsky, D. K. Inflammatory bowel disease. N. Engl. J. Med. 347, 417-429 (2002).
25. Wilmanski, J. M., Petnicki-Ocwieja, T. & Kobayashi, K. S. NLR proteins: integral members of innate immunity and mediators of inflammatory diseases. J. Leukoc. Biol. 83, 13-30 (2008).
26. Gasche, C. & Grundtner, P. Genotypes and phenotypes in Crohn’s disease: do they help in clinical management? Gut 54, 162-167 (2005).
27. Schreiber, S., Rosenstiel, P., Albrecht, M., Hampe, J. & Krawczak, M. Genetics of Crohn disease, an archetypal inflammatory barrier disease. Nat. Rev. Genet. 6, 376-388 (2005).
28. Wehkamp, J., Schmid, M., Fellermann, K. & Stange, E. F. Defensin deficiency, intestinal microbes, and the clinical phenotypes of Crohn’s disease. J. Leukoc. Biol. 77, 460-465 (2005).
29. Schmid, M. et al. Attenuated induction of epithelial and leukocyte serine antiproteases elafin and secretory leukocyte protease inhibitor in Crohn’s disease. J. Leukoc. Biol. 81, 907-915 (2007).
30. Schauber, J. et al. Heterogeneous expression of human cathelicidin hCAP18/LL-37 in inflammatory bowel diseases. Eur. J. Gastroenterol. Hepatol. 18, 615-621 (2006).
31. Wehkamp, J. et al. Inducible and constitutive beta-defensins are differentially expressed in Crohn’s disease and ulcerative colitis. Inflamm. Bowel. Dis. 9, 215-223 (2003).
32. Fahlgren, A., Hammarstrom, S., Danielsson, A. & Hammarstrom, M. L. Increased expression of antimicrobial peptides and lysozyme in colonic epithelial cells of patients with ulcerative colitis. Clin. Exp. Immunol. 131, 90-101 (2003).
33. Wehkamp, J. 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. 14, 745-752 (2002).
34. Fahlgren, A., Hammarstrom, S., Danielsson, A. & Hammarstrom, M. L. Beta-Defensin-3 and-4 in intestinal epithelial cells display increased mRNA expression in ulcerative colitis. Clin. Exp. Immunol. 137, 379-385 (2004).
35. Kiehne, K. et al. Defensin expression in chronic pouchitis in patients with ulcerative colitis or familial adenomatous polyposis coli. World J. Gastroenterol. 12, 1056-1062 (2006).
36. Fellermann, K. et al. A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am. J. Hum. Genet. 79, 439-448 (2006).
37. Kocsis, AK et al. Association of beta-defensin 1 single nucleotide polymorphisms with Crohn’s disease. Scand. J. Gastroenterol. 18, 1-9 (2007).
38. Nuding, S., Fellermann, K., Wehkamp, J., Mueller, H. A. & Stange, E. F. A flow cytometric assay to monitor antimicrobial activity of defensins and cationic tissue extracts. J. Microbiol. Methods 65, 335-345 (2006).
39. Nuding, S., Fellermann, K., Wehkamp, J. & Stange, E. F. Reduced mucosal antimicrobial activity in Crohn’s disease of the colon. Gut 56, 1240-1247 (2007).
40. Wehkamp, J. et al. NOD2 (CARD15) mutations in Crohn’ s disease are associated with diminished mucosal a-defensin expression. Gut 53, 1658-1664 (2004).
41. Kobayashi, K. S. et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307, 731-734 (2005).
42. Elphick, D., Liddell, S. & Mahida, Y. R. Impaired luminal processing of human defensin-5 in crohn’s disease: persistence in a complex with chymotrypsinogen and trypsin. Am. J. Pathol. 172, 702-713 (2008).
43. Tanabe, H. et al. Denatured human alpha-defensin attenuates the bactericidal activity and the stability against enzymatic digestion. Biochem. Biophys. Res. Commun. 358, 349-355 (2007).
44. Holler, E. et al. Prognostic significance of NOD2/CARD15 variants in HLA-identical sibling hematopoietic stem cell transplantation: effect on long-term outcome is confirmed in 2 independent cohorts and may be modulated by the type of gastrointestinal decontamination. Blood 107, 4189-4193 (2006).
45. Fishbein, T. et al. NOD2-expressing bone marrow-derived cells appear to regulate epithelial innate immunity of the transplanted human small intestine. Gut 57, 323-330 (2008).
46. Voss, E. et al. NOD2/CARD15 mediates induction of the antimicrobial peptide human beta-defensin-2. J. Biol. Chem. 281, 2005-2011 (2006).
47. Gregorieff, A. & Clevers, H. Wnt signaling in the intestinal epithelium: from endoderm to cancer. Genes Dev. 19, 877-890 (2005).
48. van Es, J. H. et al. Wnt signalling induces maturation of Paneth cells in intestinal crypts. Nat. Cell Biol. 7, 381-386 (2005).
49. Wehkamp, J. et al. The paneth cell alpha-defensin deficiency of ileal Crohn’s disease is linked to Wnt/Tcf-4. J. Immunol. 179, 3109-3118 (2007).
50. Otto, H. F. & Weitz, H. [Electron microscopy studies of Paneth cells in rats fed with zinc deficient diet]. Beitr. Pathol. 145, 336-349 (1972).
51. Cousins, R. J. A role of zinc in the regulation of gene expression. Proc. Nutr. Soc. 57, 307-311 (1998).
52. Sazawal, S. et al. Zinc supplementation in young children with acute diarrhea in India. N. Engl. J. Med. 333, 839-844 (1995).
53. Summers, R. W., Elliott, D. E., Urban, J. F. Jr., Thompson, R. & Weinstock, J. V. Trichuris suis therapy in Crohn’s disease. Gut 54, 87-90 (2005).
54. Wehkamp, J. et al. NF-kB and AP-1 mediated induction of human beta defensin-2 in intestinal epithelial cells by E. coli Nissle 1917: a novel effect of a probiotic bacterium. Infect. Immun. 72, 5750-5758 (2004).
55. Schlee, M. et al. The induction of human beta-defensin-2 by the probiotic Escherichia coli nissle 1917 is mediated through flagellin. Infect. Immun. 75, 2399-2407 (2007).
56. Kruis, W. et al. Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis. Aliment. Pharmacol. Ther. 11, 853-858 (1997).
57. Kruis, W. et al. Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut 53, 1617-1623 (2004).
58. Rembacken, B. J., Snelling, A. M., Hawkey, P. M., Chalmers, D. M. & Axon, A. T. Non-pathogenic Escherichia coli vs. mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet 354, 635-639 (1999).