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Innate Immunity and Colonic Inflammation: Enhanced Expression of Epithelial α-Defensins

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Abstract

Human α-defensins contribute to local intestinal host defense as part of innate immunity and may be of major relevance in microbial infection and chronic inflammatory bowel disease. The objective was to investigate human defensin 5 and 6 (HD-5, HD-6) mRNA expression by RT-PCR from colonic biopsies and peptide expression by immunohistochemistry from colonic resections under basal and inflammatory conditions. Both α-defensins were induced by proinflammatory cytokines in cell culture. HD-5 mRNA expression was enhanced in both idiopathic and nonidiopathic inflammatory states of the large bowel [32% of control vs 73% of unspecific colitis, 69% of Crohn’s disease (CD) and 73% of ulcerative colitis (UC)], whereas HD-6 was specifically related to CD and UC (14% in controls vs 20% in unspecific coltis, 49% in CD and 42% in UC). Immunohistochemistry confirmed the presence of HD-5 in colonic epithelium. Antimicrobial peptides in the colon may be of importance in maintaining the mucosal barrier and controlling microbial invasion in inflammatory bowel diseases.

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REFERENCES

  1. Darfeuille-Michaud A, Neut C, Barnich N, Lederman E, di Martino P, Desreumaux P, Gambiez L, Joly B, Cortot A, Colombel J-F: Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease. Gastroenterology 115:1405–1413, 1998

    PubMed  Google Scholar 

  2. D'Haens G, Geboes K, Peeters M, Baert F, Penninckx F, Rutgeerts P: Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology 114:262–267, 1998

    PubMed  Google Scholar 

  3. Harper PH, Truelove SC, Lee ECG, Kettlewell MGW, Jewell DP: Split ileostomy and ileocolostomy for Crohn's disease of the colon and ulcerative colitis: A 20-year survey. Gut 24:106–113, 1983

    PubMed  Google Scholar 

  4. Rutgeerts P, Geboes K, Peeters M, Hiele M, Penninckx F, Aerts R, Kerremans R, Vantrappen G: Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum. Lancet 338:771–774, 1991

    PubMed  Google Scholar 

  5. Duchmann R, May E, Heike M, Knolle P, Neurath M, Meyer zum Büschenfelde K-H: T cell specifity and cross reactivity towards enterobacteria, Bacteroides, Bifidobacterium, and antigens from resident intestinal flora in humans. Gut 44:812–818, 1999

    PubMed  Google Scholar 

  6. Kühn R, Löhler J, Rennick D, Rajewski K, Müller W: Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75:263–274, 1993

    PubMed  Google Scholar 

  7. Mombaerts P, Mizoguchi E, Grusby MJ, Glimcher LH, Bhan AK, Tonegawa S: Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell 75:275–282, 1993

    Google Scholar 

  8. Sadlack B, Merz H, Schorle H, Schimpl A, Feller AC, Horak I: Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell 75:253–261, 1993

    PubMed  Google Scholar 

  9. Dianda L, Hanby AM, Wright NA, Sebesteny A, Hayday AC, Owen MJ: T cell receptor-alpha beta-deficient mice fail to develop colitis in the absence of a microbial environment. Am J Pathol 150:91–97, 1997

    PubMed  Google Scholar 

  10. Elson CO, Sartor RB, Tennyson GS, Riddell RH: Experimental models of inflammatory bowel disease. Gastroenterology 109:1344–1367, 1995

    PubMed  Google Scholar 

  11. Ganz T, Lehrer RI: Defensins. Curr Opin Immunol 6:584–589, 1994

    PubMed  Google Scholar 

  12. Ouellette AJ, Hsieh MM, Nosek MT, Cano GD, Huttner KM, Buick RN, Selsted ME: Mouse Paneth cell defensins: Primary structures and antibacterial activities of numerous cryptdin isoforms. Infect Immun 62:5040–5047, 1994

    PubMed  Google Scholar 

  13. Selsted ME, Miller SI, Henschen AH, Ouellette AJ: Enteric defensins: Antibiotic peptide components of intestinal host defense. J Cell Biol 118:929–936, 1992

    PubMed  Google Scholar 

  14. Fellermann K, Stange EF: Defensins—innate immunity at the epithelial fontier. Eur J Gastroenterol Hepatol 2001 (in press)

  15. Liu L, Zhao C, Heng HH, Ganz T: The human beta-defensin-1 and alpha-defensins are encoded by adjacent genes: Two peptide families with differing disulfide topology share a common ancestry. Genomics 43:316–320, 1997

    PubMed  Google Scholar 

  16. Liu L, Wang L, Jia HP, Zhao C, Heng HHQ, Schutte BC, McCray PBJ, Ganz T: Structure and mapping of the human beta-defensin HBD-2 gene and its expression at sites of inflammation. Gene 222:237–244, 1998

    Article  PubMed  Google Scholar 

  17. Harder J, Siebert R, Zhang Y, Matthiesen P, Christophers E, Schlegelberger B, Schröder JM: Mapping of the gene encoding human beta-defensin-2 (DEFB2) to chromosome region 8p22–p23.1. Genomics 46:472–475, 1997

    PubMed  Google Scholar 

  18. Bevins CL, Jones DE, Dutra A, Schaffzin J, Muenke M: Human enteric defensin genes: Chromosomal map position and a model for possible evolutionary relationships. Genomics 31:95–106, 1996

    PubMed  Google Scholar 

  19. Diamond G, Zasloff M, Eck H, Brasseur M, Maloy WL, Bevins CL: Tracheal antimicrobial peptide, a cysteine-rich peptide from mammalian tracheal mucosa: peptide isolation and cloning of a cDNA. Proc Natl Acad Sci USA 88:3952–3956, 1991

    PubMed  Google Scholar 

  20. Schonwetter BS, Stolzenberg ED, Zasloff MA: Epithelial antibiotics induced at sites of inflammation. Science 267:1645–1648, 1995

    PubMed  Google Scholar 

  21. Tarver AP, Clark DP, Diamond G, Russell JP, Erdjument BH, Tempst P, Cohen KS, Jones DE, Sweeney RW, Wines M, Hwang S, Bevins CL: Enteric beta-defensin: Molecular cloning and characterization of a gene with inducible intestinal epithelial cell expression associated with Cryptosporidium parvum infection. Infect Immun 66:1045–1056, 1998

    PubMed  Google Scholar 

  22. Lehrer RI, Barton A, Daher KA, Harwig SS, Ganz T, Selsted ME: Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity. J Clin Invest 84:553–561, 1989

    PubMed  Google Scholar 

  23. Kagan BL, Selsted ME, Ganz T, Lehrer RI: Antimicrobial defensin peptides form voltage-dependent ion-permeable channels in planar lipid bilayer membranes. Proc Natl Acad Sci USA 87:210–214, 1990

    PubMed  Google Scholar 

  24. Jones DE, Bevins CL: Paneth cells of the human small intestine express an antimicrobial peptide gene. J Biol Chem 267:23216–23225, 1992

    PubMed  Google Scholar 

  25. Jones DE, Bevins CL: Defensin-6 mRNA in human Paneth cells: Implications for antimicrobial peptides in host defense of the human bowel. FEBS Lett 315:187–192, 1993

    PubMed  Google Scholar 

  26. Porter EM, Poles MA, Lee JS, Naitoh J, Bevins CL, Ganz T: Isolation of human intestinal defensins from ileal neobladder urine. FEBS Lett 434:272–276, 1998

    PubMed  Google Scholar 

  27. Mallow EB, Harris A, Salzman N, Russell JP, DeBerardinis RJ, Ruchelli E, Bevins CL: Human enteric defensins. Gene structure and developmental expression. J Biol Chem 271:4038–4045, 1996

    PubMed  Google Scholar 

  28. Cunliffe RN, Rose FRAJ, Keyte J, Abberley L, Chan WC, Mahida YR: 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

    PubMed  Google Scholar 

  29. Zhao C, Wang I, Lehrer RI: Widespread expression of betadefensin hBD-1 in human secretory glands and epithelial cells. FEBS Lett 396:319–322, 1996

    Article  PubMed  Google Scholar 

  30. Salzman NH, Polin RA, Harris MC, Ruchelli E, Hebra A, Zirin BS, Jawad A, Martin PE, Bevins CL: Enteric defensin expression in necrotizing enterocolitis. Pediatr Res 44:20–26, 1998

    PubMed  Google Scholar 

  31. Harder J, Bartels J, Christophers E, Schröder JM: A peptide antibiotic from human skin. Nature 387:861, 1997

    Article  PubMed  Google Scholar 

  32. Harder J, Bartels J, Christophers E, Schröder JM: Isolation and characterization of human ?-defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 276:5707–5713, 2001

    PubMed  Google Scholar 

  33. O'Neil DA, Porter EM, Elewaut D, Anderson GM, Eckmann L, Ganz T, Kagnoff MF: Expression and regulation of the human ?-defensins hBD-1 and hBD-2 in intestinal epithelium. J Immunol 163:6718–6724, 1999

    PubMed  Google Scholar 

  34. Jewell DP: In Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. M Feldman, BF Scharschmidt, MH Sleisenger (eds). Philadelphia, WB Saunders, 1998, pp 1735–1758

    Google Scholar 

  35. Kornbluth A, Sachar DB, Salomon P: In Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. M Feldman, BF Scharschmidt, MH Sleisenger (eds). Philadelphia, WB Saunders, 1998, pp 1708–1734

    Google Scholar 

  36. Stahl M, Ludwig D, Fellermann K, Stange EF: Intestinal expression of human heat shock protein 90 in patients with Crohn's disease and ulcerative colitis. Dig Dis Sci 43:1079–1087, 1998

    PubMed  Google Scholar 

  37. Ludwig D, Stahl M, Ibrahim MT, Wenzl BE, Drabicki D, Wecke A, Fellermann K, Stange EF: Enhanced intestinal expression of heat shock protein 70 in patients with inflammatory bowel disease. Dig Dis Sci 44:1440–1447, 1999

    PubMed  Google Scholar 

  38. Svinarich DM, Wolf NA, Gomez R, Gonik B, Romero R: Detection of human defensin 5 in reproductive tissues. Am J Obstet Gynecol 176:470–475, 1997

    PubMed  Google Scholar 

  39. Quayle AJ, Porter EM, Nussbaum AA, Wang YM, Brabec C, Yip KP, Mok SC.: Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract. Am J Pathol 152:1247–1258, 1998

    PubMed  Google Scholar 

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Wehkamp, J., Schwind, B., Herrlinger, K. et al. Innate Immunity and Colonic Inflammation: Enhanced Expression of Epithelial α-Defensins. Dig Dis Sci 47, 1349–1355 (2002). https://doi.org/10.1023/A:1015334917273

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