Defensinler ve H. pylori enfeksiyonundaki rolleri

Bağışıklık sistemi doğuştan ve edinsel olmak üzere iki gruba ayrılır. Doğuştan bağışıklık sistemi, edinselden farklı olarak daha önce karşılaşmadığı patojenlere karşı hızlı ve devamlı koruma sağlar. Bu sistemin başlıca üyeleri anatomik engeller, salgısal moleküller ve hücresel bileşenlerdir. Doğuştan bağışıklık sisteminin önemli bir parçası olan antimikrobiyal peptidlerin memeliler¬deki başlıca örnekleri ise defensinlerdir. Bu peptitler birçok enfeksiyonda olduğu gibi H. pylori enfeksiyonunda da görev almaktadırlar. H. pylori enfeksiyonunda defensin düzeyinin arttığı ve eradikasyonla azaldığı bilinmektedir. Ancak bu peptidlerin rolü halen net olarak ortaya konamamıştır. İleride bu konuda yapılacak çalışmalar H. pylori enfeksiyonunun patogenezini aydınlatmada yardımcı olabilir.

Anahtar Kelimeler:

Çocuk, Helicobacter pylori, Defensin, Bağışıklık, doğal

Defensins and their roles in H.Pylori infection

Immune system is divided into two groups as innate and acquired. In¬nate immune system, different from the acquired immune system, pro¬vides a quick and permanent pro¬tection against first met pathogens. The main members of this system are anatomic barriers, secretory molecules and cellular components. Leading examples of antimicrobial peptides, an important part of innate immune system, in mammals are defensins. These peptides take place in H. pylori infection like they do in many other infections. It is known that defensin level increases in H. pylori infection and decreases with eradication. On the other hand, the role of these peptides is still not clearly displayed. Studies on this subject might help to enlight the pathogenesis of H. pylori infection in the future

Keywords:

Child, Helicobacter pylori, Defensins, Immunity, Innate,

PDF

___

1. Froy O. Regulation of mammalian defensin expression by Toll-like receptor-dependent and independent signalling pathways. Cell Microbiol 2005; 7: 1387-1397.
2. Bevins CL. Paneth cell defensins: key effector molecules of innate immunity. Biochem Soc Trans 2006; 34: 263-266.
3. Dommett R, Zilbauer M, George JT, Bajaj-Elliott M. Innate immune defence in the human gastrointestinal tract. Mol Immunol 2005; 42: 903-912.
4. Fellermann K, Stange EF. Defensins- innate immunity at the epithelial frontier. Eur J Gastroenterol Hepatol 2001; 13: 771-776.
5. Zasloff M. Antimicrobial peptides of multicellular orga-nisms. Nature 2002; 415: 389-395.
6. Bevins CL, Martin-Porter E, Ganz T. Defensins and innate host defence of the gastrointestinal tract. Gut 1999; 45: 911-915.
7. Oppenheim JJ, Biragyn A, Kwak LW, Yang D. Roles of antimicrobial peptides such as defensins in innate and adaptive immunity. Ann Rheum Dis 2003; 62: 17-21.
8. De Smet K, Contreras R. Human antimicrobial peptides: defensins, cathelicidins and histatins. Biotechnol Lett 2005; 27: 1337-1347.
9. Eckmann L. Defence molecules in intestinal innate immu-nity against bacterial infections. Curr Opin Gastroenterol 2005; 21:147-151.
10. Muller CA, Autenrieth IB, Peschel A. Innate defenses of the intestinal epithelial barrier. Cell Mol Life Sci 2005; 62: 1297-1307.
11. Schneider JJ, Unholzer A, Schaller M, Schafer-Korting M, Korting HC. Human defensins. J Mol Med 2005; 83: 587-595.
12. Tosi MF. Innate immune responses to infection. J Allergy Clin Immunol 2005; 116: 241-249.
13. Yoshio H, Lagercrantz H, Gudmundsson GH, Agerberth B. First line of defense in early human life. Semin Perinatol 2004; 28: 304-311.
14. Diamond G, Bevins CL. Beta-defensins: Endogenous antibiotics of the innate host defense response. Clin Immunol Immunopathol 1998; 88: 221-225.
15. Frye M, Bargon J, Lembcke B, Wagner TO, Gropp R. Differential expression of human alpha- and beta-defen-sins mRNA in gastrointestinal epithelia. Eur J Clin Invest 2000; 30: 695-701.
16. Shai Y. Mechanism of the binding, insertion and des-tabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides. Biochim Biophys Acta 1999; 1462: 55-70.
17. Harder J, Bartels J, Christophers E, Schroder JM. Iso-lation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 2001; 276: 5707-5713.
18. Bensch KW, Raida M, Magert HJ, Schulz-Knappe P, Forssmann WG. hBD-1: a novel beta-defensin from human plasma. FEBS Lett 1995; 368: 331-335.
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 U S A. 1991; 88: 3952-3956.
20. Schonwetter BS, Stolzenberg ED, Zasloff MA. Epithelial antibiotics induced at sites of inflammation. Science 1995; 267: 1645-1648.
21. Harder J, Bartels J, Christophers E, Schroder JM. A pep-tide antibiotic from human skin. Nature 1997; 387: 861.
22. Wehkamp J, Harder J, Weichenthal M et al. Inducible and constitutive beta-defensins are differentially expressed in Crohn's disease and ulcerative colitis. Inflamm Bowel Dis 2003; 9: 215-223.
23. Lee SK, Josenhans C. Helicobacter pylori and the innate immune system. Int J Med Microbiol 2005; 295: 325–334.
24. Wada A, Mori N, Oishi K et al. Induction of human β-defensin-2 mRNA expression by Helicobacter pylori in human gastric cell line MKN45 cells on cag pathogenicity island. Biochem Biophys Res Commun 1999; 263; 770-774.
25. Isomoto H, Mukae H, Ishimoto H et al. Elevated con-centrations of alpha-defensins in gastric juice of patients with Helicobacter pylori infection. Am J Gastroenterol 2004; 99: 1916-1923.
26. George JT, Boughan PK, Karageorgiou H, Bajaj-Elliott M. Host anti-microbial response to Helicobacter pylori infection. Mol Immunol 2003; 40: 451-456.
27. Uehara N, Yagihashi A, Kondoh K et al. Human beta-defensin-2 induction in Helicobacter pylori-infected gastric mucosal tissues: antimicrobial effect of overexp-ression. J Med Microbiology 2003; 52: 41-45.
28. O’Neil DA, Cole SP, Martin-Porter E et al. Regulation of human beta-defensins by gastric epithelial cells in res-ponse to infection with Helicobacter pylori or stimulation with interleukin-1. Infect Immun 2000; 68: 5412-5415.
29. Nishi Y, Isomoto H, Mukae H et al. Concentrations of alpha- and beta-defensins in gastric juice of patients with various gastroduodenal diseases. World J Gastroenterol 2005; 11: 99-103.
30. Isomoto H, Mukae H, Ishimoto H et al. High concent-rations of human β-defensin 2 in gastric juice of patients with Helicobacter pylori infection. World J Gastroenterol 2005; 11: 4782-4787.
31. Hamanaka Y, Nakashima M, Wada A et al. Expression of human beta-defensin 2 (hBD-2) in Helicobacter pylori induced gastritis: antibacterial effect of hBD-2 against Helicobacter pylori. Gut 2001; 49: 481-487.
32. Taha AS, Faccenda E, Angerson WJ, Balsitis M, Kelly RW. Gastric epithelial anti-microbial peptides-histological correlation and influence of anatomical site and peptic ulcer disease. Dig Liver Dis 2005; 37: 51-56.
33. Wehkamp J, Schmidt K, Herrlinger KR et al. Defensin pattern in chronic gastritis: HBD-2 is differentially ex-pressed with respect to Helicobacter pylori status. J Clin Pathol 2003; 56: 352-357.
34. Wada A, Ogushi K, Kimura T et al. Helicobacter pylori-mediated transcriptional regulation of the human β-de-fensin 2 gene requires NF-κB. Cellular Microbiology 2001; 3: 115-123.
35. Hatzifoti C, Roussel Y, Harris AG, Wren BW, Morrow JW, Bajaj-Elliott M. Mucosal immunization with a urease B DNA vaccine induces innate and cellular immune respon-ses against Helicobacter pylori. Helicobacter 2006; 11: 113-122.
36. Hatzifoti C, Bajaj-Elliott M, Dorrell N et al. A plasmid immunization construct encoding urease B of Helicobac-ter pylori induces an antigen-specific antibody response and upregulates the expression of β-defensins and IL-10 in the stomachs of immunized mice. Vaccine 2004; 22: 2651-2659.