Skip to main content
SpringerLink
Log in

Upregulated Cyclooxygenase-2 Inhibits Apoptosis of Human Gastric Epithelial Cells Infected with Helicobacter pylori

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

Abstract

Helicobacter pylori induces apoptosis and alters the proliferation of gastric mucosal epithelial cells. Cyclooxygenase-2 (COX-2), the inducible form of prostaglandin (PG) synthesis, is known to cause alteration in epithelial cell growth. The goal of this study was to determine whether COX-2 gene expression by H. pylori infection could influence gastric epithelial cell apoptosis. Expression of COX-2 mRNA and proteins was up-regulated in Hs746T gastric epithelial cell lines infected with H. pylori, when assessed by quantitative RT-PCR and western blot. Inhibition of COX-2 expression using NS-398, a specific COX-2 inhibitor, showed a significant increase of gastric epithelial cell apoptosis and caspase-3 activation in Hs746T cells infected with H. pylori. Moreover, the effect of NS-398 on H. pylori-induced apoptosis was reversed by the addition of PGE2. These results suggest that up-regulated COX-2 expression by H. pylori infection can inhibit apoptosis of gastric epithelial cells.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. NIH: Consensus Development Panel on Helicobacter pylori in peptic ulcer disease. JAMA 272:65-69, 1994

    Google Scholar 

  2. Fraser AG, Sim R, Sankey EA, Dhillon AP, Pounder RE: Effect of eradication of Helicobacter pylori on gastric epithelial cell proliferation. Aliment Pharmacol Ther 8:167-173, 1994

    Google Scholar 

  3. Peek RM, Moss SF, Than KT, Perez-Perez GI, Wang S, Miller GG, Atherton JC, Holt PR, Blaser MJ: Helicobacter pylori cagA1 strains and dissociation of gastric epithelial cell proliferation from apoptosis. J Natl Cancer Inst 89:863-868, 1997

    Google Scholar 

  4. Robert JM, Searle JW, Cooksley WG: Histological patterns of prolonged hepatitis C infection. Gastroenterology 26:37-41, 1993

    Google Scholar 

  5. Zychlinsky A, Sansonetti P: Apoptosis in bacterial pathogenesis. J Clin Invest 100:493-495, 1997

    Google Scholar 

  6. Kim JM, Eckmann L, Savidge TC, Lowe DC, Witthoeft T, Kagnoff MF: Apoptosis of human intestinal epithelial cells after bacterial invasion. J Clin Invest 102:1815-1823, 1998

    Google Scholar 

  7. Hall PA, Coates PJ, Ansari A, Hopwood D: Regulation of cell number in the mammalian gastrointestinal tract: the importance of apoptosis. J Cell Sci 107:3569-3577, 1994

    Google Scholar 

  8. Moss SF, Calam J, Angarwal B, Wang S, Holt PR: Induction of gastric epithelial apoptosis by Helicobacter pylori. Gut 38:498-451, 1996

    Google Scholar 

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

    Google Scholar 

  10. Fan X, Crowe SE, Behar S, Gunasena H, Ye G, Haeberle H, van Houten N, Gourley WK, Ernst PB, Reyes VE: 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 1-mediated damage. J Exp Med 187:1659-1669, 1998

    Google Scholar 

  11. 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

    Google Scholar 

  12. Smith WL, Dewitt DL: Prostaglandin endoperoxidase H synthase-1 and-2. Adv Immunol 62:167-215, 1996

    Google Scholar 

  13. Tsujii M, DuBois RN: Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase-2. Cell 83:493-501, 1995

    Google Scholar 

  14. Tsujii M, Kawano S, DuBois RN: Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci USA 94:3336-3340, 1997

    Google Scholar 

  15. Uefuji K, Ichikura T, Mochizuki H, Shinomiya N: Expression of cyclooxygenase-2 protein in gastric adenocarcinoma. J Surg Oncol 69:168-172, 1998

    Google Scholar 

  16. Murata H, Kawano S, Tsuji S, Tsuji M, Sawaoka H, Kimura Y, Shiozaki H, Hori M: Cyclooxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma. Am J Gastroenterol 94:451-455, 1999

    Google Scholar 

  17. Eckmann L, Stenson W, Savidge TC, Lowe DC, Barrett KE, Fierer J, Smith JR, Kagnoff MF: Role of intestinal epithelial cells in the host secretory response to infection by invasive bacteria. J Clin Invest 100:296-309, 1997

    Google Scholar 

  18. Romano M, Ricci V, Memoli A, Tuccillo C, Popolo AD, Sommi P, Acquaviva AM, Del Vecchio Blanco C, Bruni CB, Zarrilli R: Helicobacter pylori up-regulates cyclooxygenase-2 mRNA expression and prostaglandin E2 synthase in MKN 28 gastric mucosal cells in vitro. J Biol Chem 273:28560-28563, 1998

    Google Scholar 

  19. Kim JS, Jung HC, Kim JM, Song IS, Kim CY: Helicobacter pylori water-soluble surface proteins activate human neutrophils and upregulate the expression of CXC chemokines. Dig Dis Sci 45:83-92, 2000

    Google Scholar 

  20. Jung HC, Kim JM, Song IS, Kim CY: Helicobacter pylori induces an array of proinflammatory cytokines in human gastric epithelial cells: quantification of mRNA for interleukin-8, 21a/b, granulocyte-macrophage colony-stimulating factor, monocyte chemoattractant protein-1 and tumor necrosis factor-a. J Gastroenterol Hepatol 12:473-480, 1997

    Google Scholar 

  21. Jobin C, Morteau O, Han DS, Sartor RB: Specific NF-kappaB blockade selectively inhibits tumour necrosis factor-alphainduced COX-2 but not constitutive COX-1 gene expression in HT-29 cells. Immunology 95:537-543, 1998

    Google Scholar 

  22. Futake N, Takahashi S, Yokoyama M, Arai I, Higuchi S, Otomo S: NS-398, a new anti-inflammatory, selectively inhibits prostaglandin G/H synthase/ cyclooxygenase (COX-2) activity in vitro. Prostaglandins 47:55-59, 1994

    Google Scholar 

  23. Bhattacharyya DK, Lecomte M, Dunn J, Morgans DJ, Smith WL: Selective inhibition of prostaglandin endoperoxide synthase-1 (cyclooxygenase-1) by valerylsalicylic acid. Arch Biochem Biophys 317:19-24, 1995

    Google Scholar 

  24. Koopman G, Reutelingsperger CP, Kuijten GA, Keehnen RM, Pals ST, van Oers MH: Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood 84:1415-1420, 1994

    Google Scholar 

  25. Zamzami, N, Marchetti P, Castedo M, Zanin C, Vayssiere JL, Petit PX, Kroemer G: Reduction in mitochondrial potential constitures an early irreversible step of programmed lymphocyte death in vivo. J Exp Med 181:1661-1672, 1995

    Google Scholar 

  26. Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH, Stemmermann GN, Nomura A: Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res 55:2111-2115, 1995

    Google Scholar 

  27. de Figueierdo Soares T, de Magalhaes Queiroz DM, Mendes EN, Rocha GA, Rocha Oliveira AM, Alvares Cabral MM, de Oliveira CA: The interrelationship between Helicobacter pylori vacuolating cytotoxin and gastric carcinoma. Am J Gastroenterol 93:1841-1847, 1998

    Google Scholar 

  28. Ristimake A, Honkanen N, Jankala H, Sipponen P, Harkonen M: Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res 57:1276-1280, 1997

    Google Scholar 

  29. Miehlke S, Go MF, Kim JG, Graham DY, Figura N: Serologic detection of Helicobacter pylori infection with cagA-positive strains in duodenal ulcer, gastric cancer, and asymptomatic gastritis. J Gastroenterol 33:18-21, 1998

    Google Scholar 

  30. Yamaoka Y, Kodama T, Gutierrez O, Kim JG, Kashima K, Graham DY: Relationship between Helicobacter pylori iceA, cagA, and vacA status and clinical outcome: Studies in four different countries. J Clin Microbiol 37:2274-2279, 1999

    Google Scholar 

  31. Jung HC, Kim JM, Song IS, Kim CY: Increased motility of Helicobacter pylori by methylcellulose could upregulate the expression of proinflammatory cytokines in human gastric epithelial cells. Scand J Clin Lab Invest 57:263-270, 1997

    Google Scholar 

  32. Elewaut D, DiDonato JA, Kim JM, Truong F, Eckmann L, Kagnoff MF: NF-kappa B is a central regulator of the intestinal epithelial cell innate immune response induced by infection with enteroinvasive bacteria. J Immunol 163:1457-1466, 1999

    Google Scholar 

  33. Keates S, Hitti YS, Upton M, Kelly CP: Helicobacter pylori infection activates NF-kappa B in gastric epithelial cells. Gastroenterology 113:1099-1109, 1997

    Google Scholar 

  34. Shift SJ, Rigas B: Nonsteroidal anti-inflammatory drugs and colorectal cancer: Evolving concepts of their chemopreventive actions. Gastroenterology 113:1992-1998, 1997

    Google Scholar 

  35. Tsujii M. Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN: Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93:705-716, 1998

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea

    Jung Mogg Kim, Joo Sung Kim, Hyun Chae Jung, In Sung Song & Chung Yong Kim

  2. Department of Internal Medicine, the Liver Research Institute, The Institutes for Endemic Diseases and the Medical Research Center, Seoul National University College of Medicine, Seoul, Korea

    Jung Mogg Kim, Joo Sung Kim, Hyun Chae Jung, In Sung Song & Chung Yong Kim

  3. Clinical Research Institute, Seoul National University Hospital, Seoul, Korea

    Jung Mogg Kim, Joo Sung Kim, Hyun Chae Jung, In Sung Song & Chung Yong Kim

Authors
  1. Jung Mogg Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joo Sung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hyun Chae Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. In Sung Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chung Yong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, J.M., Kim, J.S., Jung, H.C. et al. Upregulated Cyclooxygenase-2 Inhibits Apoptosis of Human Gastric Epithelial Cells Infected with Helicobacter pylori. Dig Dis Sci 45, 2436–2443 (2000). https://doi.org/10.1023/A:1005611613542

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1005611613542

Search

Navigation