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Helicobacter pylori Infection and Immunity pp 153–171Cite as

Apoptosis and the Pathogenesis of Helicobacter pylori—Related Disease

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Abstract

It is an unavoidable, but intriguing, fact that chronic colonization of the stomach by Helicobacter pylori has no obvious deleterious consequences in most people. Approximately 10% of all infected individuals will develop a peptic ulcer, and half of those will commence a slow progression of pre-neoplastic changes that will ultimately lead to frank cancer in only a few.1 Why are certain individuals or populations predisposed to particular clinical outcomes after infection with H. pylori? The genetic background of the individual, the timing of first infection, environmental factors, and variations in the degree of bacterial pathogenicity all may contribute to the outcome of infection. One physiologic process that can be influenced by these variables is apoptosis, which when deregulated causes abnormal cell turnover, alterations in epithelial cell subpopulations, and changes in mucosal mass.

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References

  1. Blaser M. J., and Parsonnet J. et al., 1994, Parasitism by the “slow” bacterium Helicobacter pylori leads to altered gastric homeostasis and neoplasia. J. Clin. Invest. 94:4–8

    Article  PubMed  CAS  Google Scholar 

  2. Zychlinsky A., and Sansonetti P. J. et al., 1997, Apoptosis as a proinflammatory event: What can we learn from bacteria-induced cell death? Trends in Microbiology 5:201–204

    Article  PubMed  CAS  Google Scholar 

  3. Anti M., Armuzzi A., Gasbarrini A., and Gasbarrini G. et al., 1998, Importance of changes in epithelial cell turnover during Helicobacter pylori infection in gastric carcinogenesis. Gut. 43 (suppl 1):S27–32

    Article  PubMed  Google Scholar 

  4. Shirin H., and Moss S. F. et al., 1998, Leading article: Helicobacter pylori-induced apoptosis. Gut. 43:592–594

    Article  PubMed  CAS  Google Scholar 

  5. Abdalla A. M., Krivosheyev V., Hanzely Z., Holt P. R., Perez-Perez G. I., Blaser M. J., and Moss S. F. et al., 1998, Increased epithelial cell turnover in antrum and corpus of H. pylori-infected stomach, irrespective of GagA status. Gastroenterology 114:A50

    Article  Google Scholar 

  6. Peek R. M., Moss S. F., Tham K. T., Perez-Perez G. I., Miller G. G., Atherton J. C., Holt P. R., and Blaser M.J. et al., 1997, Helicobacter pylori cagA+ strains and dissociation of gastric epithelial proliferation from apoptosis. J. Natl. Cancer Inst. 89:863–868

    Article  PubMed  CAS  Google Scholar 

  7. Rokkas T., Ladas S., Liatsos G., Petridou E., Papatheodorou G., Theocharis S., Karameris A., and Raptis S. et al., 1999, Relationship of Helicobacter pylori CagA status to gastric cell proliferation and apoptosis. Dig. Dis. Sci. 44: 487–493

    Article  PubMed  Google Scholar 

  8. Rudi J., Kuck D., Strand S., von Herbay A., Mariani S. M., Krammer P. H., Galle P. R., and Stremmel W. et al., 1998, Involvement of the GD95 (APO-1/Fas) receptor and ligand system in Helicobacter pylori-induced gastric epithelial apoptosis. J. Clin. Invest. 102:1506–1514

    Article  PubMed  CAS  Google Scholar 

  9. Houghton J., Korah R. M., Condon M. R., and Kim K. H. et al., 1999, Apoptosis in Helicobacter pylori-associated gastric and duodenal ulcer disease is mediated via the Fas antigen pathway Dig. Dis. Sci. 44:465–478

    Article  PubMed  CAS  Google Scholar 

  10. Steininger H., Faller G., Dewald E., Brabletz T., Jung A., and Kirchner T. et al., 1998, Apoptosis in chronic gastritis and its correlation with antigastric autoantibodies, only Virchows. Arch. 433:13–18

    Article  PubMed  CAS  Google Scholar 

  11. Wang T. C., Goldenring J. R., Dangler C., Ito S., Mueller A., Jeon W. K., Koh T. J., and Fox J. G. et al, 1998, Mice lacking secretory phospholipase A2 show altered apoptosis and differentiation with Helicobacterfelis infection. Gastroenterology 114:675—689

    Google Scholar 

  12. Syder A. J., Guruge J. L., Li Q., Hu Y., Oleksiewicz C. M., Lorenz R. G., Karam S. M., Falk P. G., and Gordon J. I. et al., 1999, Helicobacter pylori attaches to NeuAc alpha 2,3Gal beta 1,4 glycoconjugates produced in the stomach of transgenic mice lacking parietal cells. Mol. Cell 3:263–274

    Article  PubMed  Google Scholar 

  13. Li H., Andersson E.-M., and Helander H. F. et al., 1999, Reactions from rat gastric mucosa during one year of Helicobacter pylori infection. Dig. Dis. Sci. 44:116–124

    Article  PubMed  CAS  Google Scholar 

  14. Peek R. M., Wirth H. P., Moss S. F., Yang M., Abdalla A. M., Tham K. T., Zhang T., Tang L. H., Modlin I. M., and Blaser M. J. et al., Helicobacter pylori alters gastric epithelial cell cycle events and gastrin secretion in Mongolian gerbils. Gastroenterology (in press).

    Google Scholar 

  15. Li M., Mellgard B., and Helander H. F. et al., 1997, Inoculation of VacA- and CagA-Helicobacter pylori delays gastric ulcer healing in the rat. Scand. J. Gastroenterol. 32:439–444

    Article  PubMed  CAS  Google Scholar 

  16. Piotrowski J., Piotrowski E., Skrodzka D., Slomiany A., and Slomiany B. L. et al., 1997, Induction of acute gastritis and epithelial cell apoptosis by Helicobacter pylori lipopolysaccharide. Scand. J. Gastroenterol. 32:203–211

    Article  PubMed  CAS  Google Scholar 

  17. Aliprantis A. O., Yang R.-B., Mark M. R., Suggett S., Devaux B., Radolf J. D., Klimpel G. R., Godowski P., and Zychlinsky A. et al., 1999, Cell activation and apoptosis by bacterial lipoproteins through Toll-like receptor-2. Science 285:736–739

    Article  PubMed  CAS  Google Scholar 

  18. Luo X.-L., Ramanujam K. S., Zhao H.-M., Moss S. F., Russell R. G., Drachenberg C. B., and Wilson K. T. et al., 1999, Protective role of GOX-2 in H. pylori gastritis. Gastroenterology 116:A767

    Google Scholar 

  19. Fox J. G., Li X., Cahill R. J., Andrutis K., Rustgi A. K., Odze R., and Wang T. G. et al., 1996, Hypertrophic gastropathy in Helicobacter felis-infected wild-type C57BL/6 mice and p53 hemizy-gous transgenic mice. Gastroenterology 110:155–166

    Article  PubMed  CAS  Google Scholar 

  20. Lozniewski A., Muhale F., Hatier R., Marais A., Conroy M. C., Edert D., le Faou A., Weber M., and Duprez A. et al., 1999, Human embryonic gastric xenografts in nude mice: a new model of Helicobacter pylori infection. Infect. Immun. 67:1798–1805

    PubMed  CAS  Google Scholar 

  21. Crabtree J. E., Farmery S. M., Lindley I. J., Peichl P., and Tompkins D. S. et al., 1994, CagA/cytotoxic strains of Helicobacter pylori and interleukin-8 in gastric epithelial cell lines. J. Clin. Pathol. 47:945–950

    Article  PubMed  CAS  Google Scholar 

  22. Sharma S. A., Tummuru M. K. R., Miller G. G., and Blaser M. J. et al., 1995, Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro. Infect. Immun. 63:1681–1687

    PubMed  CAS  Google Scholar 

  23. Ogura K., Takahashi M., Maeda S., Ikenoue T., Kanai F., Yoshida H., Shiratori Y., Mori K., Mafune K. I., and Ogata M. et al., 1998, Interleukin-8 production in primary cultures of human gastric epithelial cells induced by Helicobacter pylori. Dig. Dis. Sci. 43:2738–2743

    Article  PubMed  CAS  Google Scholar 

  24. Beales I. L., and Calam J. et al., 1997, Stimulation of IL-8 production in human gastric epithelial cells by Helicobacter pylori, IL-1 beta and TNF-alpha requires tyrosine kinase activity, but not protein kinase G. Cytokine 9:514–520

    Article  PubMed  CAS  Google Scholar 

  25. Aihara M., Tsuchimoto D., Takizawa H., Azuma A., Wakebe H., Ohmoto Y., Imagawa K., Kikuchi M., Mukaida N., and Matsushima K. et al., 1997, Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45. Infect. Immun. 65:3218–3224

    PubMed  CAS  Google Scholar 

  26. Segal E. D., Lange G., Govacci A., Tompkins L. S., and Falkow S. et al., 1997, Induction of host signal transduction pathways by Helicobacter pylori. Proc. Natl. Acad. Sci. USA 94:7595–7599

    Article  PubMed  CAS  Google Scholar 

  27. Sharma S. A., Tummuru M. K., Blaser M. J., and Kerr L. D. et al., 1998, Activation of IL-8 gene expression by Helicobacter pylori is regulated by transcription factor nuclear kappa B in gastric epithelial cells. J. Immunol. 160:2401–2407

    PubMed  CAS  Google Scholar 

  28. Terui Y., Tomizuka H., Mishima Y., Ikeda M., Kasahara T., Uwai M., Mori M., Itoh T., Tanaka M., Yamada M., Shimamura S., Ishizaka Y., Ozawa K., and Hatake K. et al., 1999, Cancer Res. 59:5651–5655

    PubMed  CAS  Google Scholar 

  29. Chen G., Sordillo E. M., Ramey W. G., Reidy J., Holt P., Krajewski S., Reed J. C., Blaser M. J., and Moss S. F. et al., 1997, Apoptosis in gastric epithelial cells is induced by Helicobacter pylori and accompanied by increased expression of BAK. Biochem. Biophys. Res. Commun. 239:626–632

    Article  PubMed  CAS  Google Scholar 

  30. Tummuru M. K., Sharma S. A., and Blaser M. J. et al., 1995, Helicobacter pylori picB, a homologue of the Bordetella pertussis toxin secretion protein, is required for the induction of IL-8 in gastric epithelial cells. Mol. Microbiol. 18:867–876

    Article  PubMed  CAS  Google Scholar 

  31. Censini S., Lange C., Xiang Z., Crabtree J. E., Ghiara P., Borodovsky M., Rappuoli R., and Covacci A. et al., 1996, cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc. Natl. Acad. Sci. USA 93:14648–14653

    Article  PubMed  Google Scholar 

  32. Munzenmaier A., Lange G., Glocker E., Govacci A., Moran A., Bereswill S., Baeuerle P. A., Kist M., and Pahl H. L. et al., 1997, A secreted/shed product of Helicobacter pylori activates transcription factor nuclear factor kappa B. J. Immunol. 159:6140–6147

    PubMed  CAS  Google Scholar 

  33. Keates S., Keates A. C., Warney M., Peek R. M., Murray P. G., and Kelly C. P. et al., 1999, Differential activation of mitogen-activated protein-kinases in AGS epithelial cells by cag+ and cag- Helicobacter pylori. J. Immunol. 163:5552–5559

    PubMed  CAS  Google Scholar 

  34. Peek R. M., Blaser M. J., Mays D. J., Forsyth M. H., Cover T. L., Song S. Y., Krishnan U., and Pietenpol J. A. et al.,Helicobacter pylori strain-specific genotypes and modulation of the gastric epithelial cell cycle. Cancer Res. (in press)

    Google Scholar 

  35. Wagner S., Beil W., Westermann J., Logan R. P., Bock C. T., Trautwein C., Bleck J. S., and Manns M. P. et al., 1997, Regulation of gastric epithelial cell growth by Helicobacter pylori: evidence for a major role of apoptosis. Gastroenterology 113:1836–1847

    Article  PubMed  Google Scholar 

  36. Kimura M., Gotot S., Wada A., Yahiro K., Niidome T., Hatakeyama T., Aoyagi H., Hirayama T., and Kondo T et al., 1999, Vacuolating cytotoxin purified from Helicobacter pylori causes mitochondrial damage in human gastric cells. Microb. Pathog. 26:45–52

    Article  PubMed  CAS  Google Scholar 

  37. Pai R., Cover T. L., and Tarnawski A. S. et al., 1999, Helicobacter pylori vacuolating cytotoxin (VacA) disorganizes the cytoskeletal architecture of gastric epithelial cells. Biochem. Biophys. Res. Commun. 19:245–250

    Google Scholar 

  38. Papini E., Satin B., Norais N., deBernard M., Telford J. L., Rappuoli R., and Montecucco C. et al., 1998, Selective increase of the permeability of polarized epithelial cell monolayers by Helicobacter pylori vacuolating toxin. J. Clin. Invest. 102:813–820

    Article  PubMed  CAS  Google Scholar 

  39. Pellici V., Reyrat J. M., Sartori L., Pagliaccia C., Rappuoli R., Telford J. L., Montecucco C., and Papini E. et al., 1999, Helicobacter pylori VacA cytotoxin associated with the bacteria increases epithelial permeability independently of its vacuolating activity. Microbiology 145:2043–2050

    Article  Google Scholar 

  40. Manetti R., Massari P., Marchetti M., Magagnoli C., Nuti S., Lupetti P., Ghiara P., Rappuoli R., and Telford J. L. et al, 1997, Detoxification of the Helicobacter pylori cytotoxin. Infect. Immun. 65:4615–4619

    PubMed  CAS  Google Scholar 

  41. Shibata J., Goto H., Arisawa T., Niwa Y, Hayakawa T., Nakayama A., and Mori N. et al., 1999, Regulation of tumour necrosis factor (TNF) induced apoptosis by soluble TNF receptors in Helicobacter pylori infection. Gut. 45:24—31

    Article  PubMed  CAS  Google Scholar 

  42. Jones N. L., Day A. S., Jennings H. A., and Shernman P. M. et al.,1999, Helicobacter pylori induces gastric epithelial cell apoptosis in association with increased Fas receptor expression. Infect. Immun. 67:4237–4242

    PubMed  CAS  Google Scholar 

  43. Fan X., Crowe S. F., Behar S., Gunasena H., Ye G., Haeberle H., Van Houten N., Gourley W. K., Ernst P. B., and Reyes V. E. et al., 1998, The effect of class II major histocompatibility complex expression on adherence of Helicobacter pylori and induction of apoptosis in gastric epithelial cells: A mechanism for T helper cell type-I mediated damage. J. Exp. Med. 187: 1659–1669

    Article  PubMed  CAS  Google Scholar 

  44. Konturek P. C., Pierzchalski P., Konturek S. J., Meixner H., Faller G., Kirchner T., and Hahn E. G. et al, 1999, Helicobacter pylori induces apoptosis in gastric mucosa through an upregulation of Bax expression in humans. Scand. J. Gastroenterol. 34:375–383

    Article  PubMed  CAS  Google Scholar 

  45. Wagner S., Mix H., Sobek-Koocked I., Obst B., Schmidt H., Bleck J., Kirchner G., Gokeb M., Manns M. P., and Beil W. et al., 1999, Activation of caspase-8 and -3 mediates apoptosis in gastric epithelial cells induced by Helicobacter pylori. Gastroenterology 116:347

    Google Scholar 

  46. Naumann M. Wessler S., Bartsch C., Wielans B., Covacci A., Haas R., and Meyer T F. et al., 1999, Activation of activator protein-1 and stress response kinases in epithelial cells colonized by Helicobacter pylori encoding the pathogenicity island. J. Biol. Chem. 274:31655–31662

    Article  PubMed  CAS  Google Scholar 

  47. Wisdom R., Johnson R. S., and Moore C. et al.,1999, c-Jun regulates cell cycle progression and apoptosis by distinct mechanisms. EMBO J. 18:188–197

    Article  PubMed  Google Scholar 

  48. Holtmann H., Winzen R., Holland P., Eickemeier S., Hoffman E., Wallack D., Malinin N. L., Cooper J. A., Resch K., and Kracht M. et al., 1999, Induction of Interleukin-8 synthesis integrates effects on transcription and mRNA degradation from at least three different cytokine- or stress-activated signal transduction pathways. Mol. Cell Biol. 19:6742–6753

    PubMed  CAS  Google Scholar 

  49. Shirin H., Sordillo E. M., Oh S. H., Yamamoto H., Delohery T., Weinstein I. B., and Moss S. F. et al, 1999, Helicobacter pylori inhibits the G1 to S transition in AGS gastric epithelial cells. Cancer Res. 59:2277–2281

    PubMed  CAS  Google Scholar 

  50. Knipp U., Birkholz S., Kaup W., and Opferkuch W. et al., 1996, Partial characterization of a cell proliferation inhibiting protein produced by Helicobacter pylori. Infect. Immun. 64:3491–3496

    PubMed  CAS  Google Scholar 

  51. Shenker B. J., and Datar S. et al., 1995, Fusobacterium nucleatum inihibits T cell activation by arresting cells in the mid Gl phase of the cell cycle. Infect. Immun. 63:4830–4836

    PubMed  CAS  Google Scholar 

  52. Shirin H., Sordillo E. M., Delohery T., Weinstein I. B., and Moss S. F et al., 1999, Reduced expression of the cyclin-dependent kinase inhibitor, p27kipl in subclones of AGS gastric epithelial cells resistant to H. jfry/on-induced apoptosis. Gastroenterology 116:A503

    Article  Google Scholar 

  53. Lloyd R. V., Erikson L. A., Jin L., Kulig E., Qian X., Cheville J. C., and Scheithauer B. W. et al.,1999, p27kipl: A multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancer. Am. J. Pathology 154:313–323

    Article  Google Scholar 

  54. Fero M. L., Randel E., Gurley K. E., Roberts J. M., and Kemp C. J. et al., 1998, The murine gene p27kipl is haplo-insufficient for tumour suppression. Nature 396:177–180

    Article  PubMed  CAS  Google Scholar 

  55. Doig P., and Trust T. J. et al., 1997, The molecular basis for H. pylori adherence and colonization, in: The Immunobiology of H. pylori: From Pathogenesis to Prevention, PB Ernst, P Michetti, PD Smith, eds., Lippincott-Raven, Philadelphia

    Google Scholar 

  56. Ilver D., Arnqvist A., Ogren J., Frick I.-M., Kersulyte D., Incecik E. T, Berg D. E., Covacci A., Engstrand L., and Borens T. et al., 1998, Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by re tagging. Science 279:373–377

    Article  PubMed  CAS  Google Scholar 

  57. Ishida M., Gomyo Y., Ttaebe S., Ohfuji S., and Ito H. et al., 1996, Apoptosis in human gastric mucosa, chronic gastritis, dysplasia and carcinoma: analysis by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling. Virchows. Arch. 428:229–235

    Article  PubMed  CAS  Google Scholar 

  58. Moss S. F., Valle J., Abdalla A. M., Wang S., Siurala M., and Sipponen P. et al., 1999, Gastric cellular turnover and the development of atrophy after 31 years of follow up: a case-control study. Am. J. Gastroenterology 94:2109–2114

    Article  CAS  Google Scholar 

  59. Yabuki N., Sasano H., Tobita M., Imatani A., Hoshi T., Kato K., Ohara S., Asaki S., Toyota T., and Nagura H. et al., 1997, Analysis of cell damage and proliferation in Helicobacterpylori-mkcted human gastric mucosa from patients with gastric adenocarcinoma. Am. J. Pathol. 151:821–829

    PubMed  CAS  Google Scholar 

  60. Lauwers G. Y., Scott G. V., and Karpeh M. S. et al., 1995, Immunohistochemical evaluation of bcl-2 protein expression in gastric adenocarcinomas. Cancer 75:2209–2213

    Article  PubMed  CAS  Google Scholar 

  61. Kondo Shinomura Y., Kanayama S., Higashimoto Y., Miyagawa J. L., Minami T., Kiyohara T., Zushi S., Kitamura S., Isozaki K., and Matsuzawa Y. et al., 1996, Over-expression of Bcl-XL gene in human gastric adenomas and carcinomas. Int. J. Cancer 68:727–730

    Article  Google Scholar 

  62. Krajewska M., Fenoglio-Preiser C. M., Song K., Macdonald J. S., Stemmerman G., and Reed J. C. et al., 1996, Immunohistochemical analysis of the Bcl-2 family proteins in adenocarcinoma of the stomach. Am. J. Pathol. 149:1449–1457

    PubMed  CAS  Google Scholar 

  63. Lu G.-D., Altieri D. C., and Tanigawa N. et al., 1998, Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res. 58:1808–1812

    CAS  Google Scholar 

  64. Bennett M. W., O’Connell J., O’SuUivan G. C., Roche D., Brady C., Kelly J., Collins J. K., and Shanahan F. et al., 1999, Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer. Gut. 44:156–162

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology & Laboratory Medicine , USA

    Emilia Mia Sordillo

  2. Department of Medicine, St. Luke’s-Roosevelt Hospital Center/Columbia University New York, NY, 10025, USA

    Emilia Mia Sordillo & Steven F. Moss

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  1. Emilia Mia Sordillo
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  2. Steven F. Moss
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  1. University of South Florida College of Medicine, Tampa, Florida, USA

    Yoshimasa Yamamoto  & Herman Friedman  & 

  2. Dalhousie University, Halifax, Nova Scotia, Canada

    Paul S. Hoffman

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Sordillo, E.M., Moss, S.F. (2002). Apoptosis and the Pathogenesis of Helicobacter pylori—Related Disease. In: Yamamoto, Y., Friedman, H., Hoffman, P.S. (eds) Helicobacter pylori Infection and Immunity. Infectious Agents and Pathogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0681-2_10

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