Skip to main content
Log in

Helicobacter pylori and Acetylsalicylic Acid Synergistically Accelerate Apoptosis via Fas Antigen Pathway in Rabbit Gastric Epithelial Cells

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The mechanism for gastric epithelial cellular apoptosis by both H. pylori and NSAIDs remains unknown. Normal gastric epithelial cells, collected from rabbit stomach, were cultured with viable H. pylori and/or an acetylsalicylic acid for 24 hr as an in vitro model of gastric epithelial cell injury. The Fas antigen expression rate in the gastric epithelial cells was measured using a FACScan. In group E, in which H. pylori inoculation of epithelial cells was followed by treatment with an NSAID, the rate of Fas antigen expression was significantly higher than the rate observed after treatment with either H. pylori or NSAID alone. Despite the fact that drug treatment alone did not significantly increase the Fas expression rate vs control cells. The results suggest that H. pylori and NSAID induce gastric cell injury as apoptosis via the Fas antigen pathway in a synergistic manner and that this effect is particularly strong when NSAID treatment follows H. pylori infection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Hopkins RJ, Girardi LS, Turney EA: Relationship between Helicobacter pylori eradication and reduced duodenal and gastric ulcer recurrence: A review. Gastroenterology 110:1244–1252, 1996

    PubMed  Google Scholar 

  2. McCarthy DM: Mechanisms of mucosal injury and healing: The role of non-steroidal anti-inflammatory drugs. Scand J Gastroenterol 208:498–501, 1995

    Google Scholar 

  3. Derry S, Loke YK: Risk of gastrointestinal haemorrhage with long term use of aspirin: Meta-analysis. BMJ 321:1170–1171, 2000

    PubMed  Google Scholar 

  4. Chan FK, Sung JJ, Chung SC, To KF, Yung MY, Leung VK, Lee YT, Chan CS, Li EK, Woo J: Randomised trial of eradication of Helicobacter pylori before non-steroidal antiinflammatory drug therapy to prevent peptic ulcers. Lancet 350:975–979, 1997

    PubMed  Google Scholar 

  5. Santucci L, Fiorucci S, Patoia L, Di Matteo FM, Brunori PM, Morelli A: Severe gastric mucosal damage induced by NSAIDs in healthy subjects is associated with Helicobacter pylori infection and high levels of serum pepsinogens. Dig Dis Sci 40:2074–2080, 1995

    PubMed  Google Scholar 

  6. Graham DY, Lidsky MD, COX AM, Evans DJ, Evans DG, Alpert L, Klein PD, Sessoms SL, Michaletz PA, Saeed ZA: Long-term nonsteroidal anti-inflammatory drug use and Helicobacter pylori infection. Gastroenterology 100:1653–1657, 1991

    PubMed  Google Scholar 

  7. Hawkey CJ, Tulassay Z, Szczepanski L, van Rensburg CJ, Filipowicz-Sosnowska A, Lanas A, Wason CM, Peacock RA, Gillon KRW: Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study. Lancet 352:1016–1021, 1998

    PubMed  Google Scholar 

  8. Wagner S, Beil W, Westermann J, Logan RP, Bock CT, Trautwein C, Bleck JS, Manns MP: Regulation of gastric epithelial cells growth by Helicobacter pylori: Evidence for a major role of apoptosis. Gastroenterology 113:1836–1847, 1997

    PubMed  Google Scholar 

  9. Tanaka M, Ito H, Adachi S, Akimoto H, Nishikawa T, Kasajima T, Marumo F, Hiroe M: Hypoxia induces apoptosis with enhanced expression of Fas antigen messenger RNA in cultured neonatal rat cardiomyocytes. Circ Res 75:426–433, 1994

    PubMed  Google Scholar 

  10. Rudi J, Kuck D, Strand S, von Herbay A, Mariani SM, Krammer PH, Galle PR, Stremmel W: Involvement of the CD95 (APO-1/Fas) receptor and ligand system in Helicobacter pylori-induced gastric epithelial apoptosis. J Clin Invest 102:1506–1514, 1998

    PubMed  Google Scholar 

  11. Yonehara S, Ishii A, Yonehara M: A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J Exp Med 169:1747–1756, 1989

    Article  PubMed  Google Scholar 

  12. Covacci A, Censini S, Bugnoli M, Petracca R, Burroni D, Macchia G, Massone A, Papini E, Xiang Z, Figura N, Rappuoli R: Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci USA 90:5791–5795, 1993

    PubMed  Google Scholar 

  13. Cover TL, Tummuru MKR, Cao P, Thompson SA, Blaser MJ: Divergence of genetic sequences for vacuolating cytotoxin among Helicobacter pylori strains. J Biol Chem 269:10566–10573, 1994

    PubMed  Google Scholar 

  14. Phadnis SH, Ilver D, Janzon L, Normark S, Westblom TU: Pathological significance and molecular characterization of the vacuolating toxin gene of Helicobacter pylori. Infect Immun 62:1557–1565, 1994

    PubMed  Google Scholar 

  15. Awakawa T, Sugiyama T, Hisano K, Karita M, Yachi A: Detection and identification of cagA of Helicobacter pylori by polymerase chain reaction. Eur J Gastroenterol Hepatol 7(suppl 1):S75–S78, 1995

    PubMed  Google Scholar 

  16. Ueda F, Kyoi T, Mimura K, Kimura K, Yamamoto M: Intercellular communication in cultured rabbit gastric epithelial cells. Jpn J Phamacol 57:321–328, 1991

    Google Scholar 

  17. Towbin H, Staehelin T, Gordon J: Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some application. Proc Natl Acad Sci USA 76:4350–4354, 1979

    PubMed  Google Scholar 

  18. Wyllie AH: Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284:555–556, 1980

    PubMed  Google Scholar 

  19. Lanza FL, Evans DG, Graham DY: Effect of Helicobacter pylori infection on the severity of gastroduodenal mucosal injury after the acute administration of naproxen or aspirin to normal volunteers. Am J Gastroenterol 86:735–737, 1991

    PubMed  Google Scholar 

  20. French LE, Hahne M, Viard I, Radlgruber G, Zanone R, Becker K, Muller C, Tschopp J: Fas and Fas ligand in embryos and adult mice: Ligand expression in several immuneprivileged tissues and co-expression in adult tissues characterized by apoptotic cell turnover. J Cell Bio 133:335–343, 1996

    Google Scholar 

  21. Houghton J, Korah RM, Condon MR, Kim KH: Apoptosis in Helicobacter pylori-associated gastric and duodenal ulcer disease is mediated via the Fas antigen pathway. Dig Dis Sci 44:465–478, 1999

    PubMed  Google Scholar 

  22. Kim JM, Kim JS, Jung HC, Song IS, Kim CY: Apoptosis of human gastric epithelial cells via caspase-3 activation in response to Helicobacter pylori infection: Possible involvement of neutrophils through tumor necrosis factor alpha and soluble Fas ligands. Scand J Gastroenterol 35:40–48, 2000

    PubMed  Google Scholar 

  23. Shirin H, Moss SF: Helicobacter pylori induced apoptosis. Gut 43:592–594, 1998

    PubMed  Google Scholar 

  24. Moss SF, Calam J, Agarwal B, Wang S, Holt PR: Induction of gastric epithelial apoptosis by Helicobacter pylori. Gut 38:498–501, 1996

    PubMed  Google Scholar 

  25. Crabtree JE, Farmery SM, Lindley IJD, Figura N, Peichl P, Tompkins DS: CagA/cytotoxin strains of Helicobacter pylori and interleukin-8 in gastric epithelial cell lines. J Clin Pathol 47:945–950, 1994

    PubMed  Google Scholar 

  26. Santucci L, Fiorucci S, Giansanti M, Brunori PM, Di Matteo FM, Morelli A: Pentoxifylline prevents indomethacin induced acute gastric mucosal damage in rats: Role of tumor necrosis factor alpha. Gut 35:909–915, 1994

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Watanabe, K., Hoshiya, S., Tokunaga, K. et al. Helicobacter pylori and Acetylsalicylic Acid Synergistically Accelerate Apoptosis via Fas Antigen Pathway in Rabbit Gastric Epithelial Cells. Dig Dis Sci 47, 809–817 (2002). https://doi.org/10.1023/A:1014752303138

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1014752303138

Navigation