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Helicobacter pylori extract induces nuclear factorkappa b, activator protein-1, and cyclooxygenase-2 in esophageal epithelial cells

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Journal of Gastrointestinal Surgery

Abstract

Helicobacter pylori infection is recognized as the major cause of gastritis and gastric cancer; however, its role in the development of gastroesophageal reflux disease and Barrett’s adenocarcinoma is unclear. The expression of NF-кB, AP-1, and COX-2 may be important in inflammation and tumorigenesis in the esophagus. The aim of this study was to examine the effect of live H pylori or H pylori extract (HPE) on these factors in the esophageal epithelial cell lines SKGT-4 and OE33. NF-кB and AP-1 activity were assessed by gel shift assay and COX-2 by Western blotting. Coculture of SKGT-4 and OE33 with live H pylori and HPE induced NF-кB and AP-1 DNA-binding activity, and also decreased IкB-α levels. Treatment with the specific MEK1/2 MAPK inhibitor PD98059, but not the p38 MAPK inhibitor SB203580, inhibited NF-кB and AP-1 activity. The antioxidant vitamin C inhibited H pylori-induced NF-кB activation, but increased AP-1 expression. Moreover, HPE induced COX-2 expression and IL-8 production, and PD98059 inhibited COX-2 expression, ERK1/2 phosphorylation, and IL-8 production. These data demonstrate that both live H pylori and HPE induce NF-к B and AP-1 expression in esophageal epithelial cells. The induction of such transcription factors may play a role in the specific immune response within Barrett’s mucosa and may indirectly cause inflammation of the gastric cardia and the distal esophagus.

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References

  1. Parsonnet J. Helicobacter pylori: The size of the problem. Gut 1998;43(Suppl 1):S6.

    Article  PubMed  Google Scholar 

  2. Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 7–14 June 1994. IARC Monogr Eval Carcinog Risks Hum 1994;61:1-241.

    Google Scholar 

  3. Hosking SW, Ling TK, Chung SC, et al. Duodenal ulcer healing by eradication of Helicobacter pylori without antiacid treatment. Randomised controlled trial. Lancet 1994; 343:508–510.

    Article  PubMed  CAS  Google Scholar 

  4. Torrado J, Ruiz B, Garay J, et al. Blood-group phenotypes, sulfomucins, and Helicobacter pylori in Barrett’s esophagus. Am J Surg Pathol 1997;21:1023–1029.

    Article  PubMed  CAS  Google Scholar 

  5. Wright TA, Myskow M, Kingsnorth AN. Helicobacter pylori colonization of Barrett’s esophagus and its progression to cancer. Dis Esophagus 1997;10:196–200.

    PubMed  CAS  Google Scholar 

  6. Goldblum JR, Vicari JJ, Falk GW, et al. Inflammation and intestinal metaplasia of the gastric cardia: The role of gastroesophageal reflux and H pylori infection. Gastroenterology 1998;114:633–639.

    Article  PubMed  CAS  Google Scholar 

  7. Voutilainen M, Farkkila M, Mecklin JP, Juhola M, Sipponen P. Chronic inflammation at the gastroesophageal junction (carditis) seems to be a specific finding related to Helicobacter pylori infection and gastroesophageal reflux disease. The Central Finland Endoscopy Study Group. Am J Gastroenterol 1999;94:3175–3180.

    Article  PubMed  CAS  Google Scholar 

  8. Graham DY. Helicobacter pylori infection in the pathogenesis of duodenal ulcer and gastric cancer: A model. Gastroenterology 1997;113:1983–1991.

    Article  PubMed  CAS  Google Scholar 

  9. El-Omar EM, Oien K, El-Nujumi A, et al. Helicobacter pylori infection and chronic gastric acid hyposecretion. Gastroenterology 1997;113:15–24.

    Article  PubMed  CAS  Google Scholar 

  10. Manes G, Mosca S, Laccetti M, Lioniello M, Balzano A. Helicobacter pylori infection, pattern of gastritis, and symptoms in erosive and nonerosive gastroesophageal reflux disease. Scand J Gastroenterol 1999;34:658–662.

    Article  PubMed  CAS  Google Scholar 

  11. Labenz J, Malfertheiner P. Helicobacter pylori in gastrooesophageal reflux disease: Causal agent, independent or protective factor? Gut 1997;41:277–280.

    Article  PubMed  CAS  Google Scholar 

  12. Vicari JJ, Peek RM, Falk GW, et al. The seroprevalence of cagA-positive Helicobacter pylori strains in the spectrum of gastroesophageal reflux disease. Gastroenterology 1998; 115:50–57.

    Article  PubMed  CAS  Google Scholar 

  13. Chow WH, Blaser MJ, Blot WJ, et al. An inverse relation between cagAC strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma. Cancer Res 1998;58:588–590.

    PubMed  CAS  Google Scholar 

  14. Kopp EB, Ghosh S. NF-kB and Rel proteins in innate immunity. Adv Immunol 1995;58:1–27.

    Article  PubMed  CAS  Google Scholar 

  15. Baeuerle PA, Henkel T. Function and activation of NF-kB in the immune system. Annu Rev Immunol 1994;12:141–179.

    Article  PubMed  CAS  Google Scholar 

  16. Abdel-Latif MM, O’Riordan J, Windle HJ, et al. NF-kappaB activation in esophageal adenocarcinoma: Relationship to Barrett’s metaplasia, survival, and response to neoadjuvant chemoradiotherapy. Ann Surg 2004;239:491–500.

    Article  PubMed  Google Scholar 

  17. Jones AD, Bacon KD, Jobe BA, Sheppard BC, Deveney CW, Rutten MJ. Helicobacter pylori induces apoptosis in Barrett’s-derived esophageal adenocarcinoma cells. J Gastrointest Surg 2003;7:68–76.

    Article  PubMed  Google Scholar 

  18. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1979;72:248–254.

    Article  Google Scholar 

  19. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970;297:680–685.

    Article  Google Scholar 

  20. Osborn L, Kunkel S, Nabel GJ. Tumor necrosis factor alpha and interleukin-1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Pro Natl Acad Sci USA 1989;86:2336–2340.

    Article  CAS  Google Scholar 

  21. Whitmarsh AJ, Davis RJ. Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J Mol Med 1996;74:589–607.

    Article  PubMed  CAS  Google Scholar 

  22. Cave DR, Vargas M. Effect of a Campylobacter pylori protein on acid secretion by parietal cells. Lancet 1989;ii:187–189.

    Article  Google Scholar 

  23. Konturek SJ, Konturek PJ, Brzozowski T, Stachnura J, Zombala M. Gastric mucosal damage and adaptive protection by ammonia and ammonium ions in rats. Digestion 1996;57:433–445.

    Article  PubMed  CAS  Google Scholar 

  24. Kim JS, Kim JM, Jung HC, Song IS. Expression of cyclooygenase-2 in human neutophils activated by Helicobacter pylori water-soluble proteins: Possible involvement of NFkappaB and MAP kinase signalling pathway. Dig Dis Sci 2001;46:2277–2284.

    Article  PubMed  CAS  Google Scholar 

  25. Matsumoto K, Hashimoto S, Gon Y, Nakayama T, Horie T. Proinflammatory cytokine-induced and chemical mediatorinduced IL-8 expression in human bronchial epithelial cells through p38 mitogen-activated protein kinase-dependent pathway. J Allergy Clin Immunol 1998;101:825–831.

    Article  PubMed  CAS  Google Scholar 

  26. Laine L, Cominelli F, Sloane R, Casini-Raggi V, Marin- Sorensen M. Interaction of NSAIDs and Helicobacter pylori on gastrointestinal injury and prostaglandin production: A controlled double-blind trial. Aliment Pharmacol Ther 1995;9:127–135.

    Article  PubMed  CAS  Google Scholar 

  27. Wilson KT, Ramanujam KS, Mobley HLT, Musselman RF, James SP, Meltzer SJ. Helicobacter pylori stimulates inducible nitric oxide synthase expression and activity in a murine macrophage cell line. Gastroenterology 1996;111:1524–1533.

    Article  PubMed  CAS  Google Scholar 

  28. Noach LA, Bosma NB, Jansen J, Hoek FJ, van Deventer SJ, Tytgat GN. Mucosal tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8 production in patients with Helicobacter pylori infection. Scand J Gastroenterol 1994; 29:425–429.

    Article  PubMed  CAS  Google Scholar 

  29. Genta RM, Huberman RM, Graham DY. The gastric cardia in Helicobacter pylori infection. Hum Pathol 1994;25:915–919.

    Article  PubMed  CAS  Google Scholar 

  30. Preikseitis HG, Tremblay L, Diamant NE. Nitric oxide mediates inhibitory nerve effects in human esophagus and lower esophageal sphincter. Dig Dis Sci 1994;39:770–775.

    Article  Google Scholar 

  31. Mukhopadhyyay A, Rattan S, Goyal RK. Effect of prostaglandin E2 on esophageal motility in man. J Appl Physiol 1975;39:479–481.

    Google Scholar 

  32. Keates S, Hitti YS, Upton M, Kelly CP. Helicobacter pylori infection activates NF-кB in gastric epithelial cells. Gastroenterology 1998;113:1099–1109.

    Article  Google Scholar 

  33. Wetscher GJ, Hinder PR, Bagchi D, et al. Free radical scavengers prevent reflux esophagitis in rats. Dig Dis Sci 1995; 40:1292–1296.

    Article  PubMed  CAS  Google Scholar 

  34. Oh TY, Lee JS, Ahn BO, et al. Oxidative stress is more important than acid in the pathogenesis of reflux oesophagitis in rats. Gut 2001;49:364–371.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery and Clinical Medicine, Trinity Centre for Health Sciences, St. James’s Hospital, Dublin, Ireland

    Mohamed M.M. Abdel-Latif Ph.D. & John V. Reynolds M.D.

  2. Dublin Molecular Medicine Centre, Trinity Centre for Health Sciences, St. James’s Hospital, Dublin, Ireland

    Henry Windle Ph.D., Ana Terres Ph.D. & Déirdre Ní Eidhin Ph.D.

  3. Department of Surgery, Trinity Centre for Health Sciences, St. James’s Hospital, Dublin 8, Ireland

    Dermot Kelleher M.D.

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  1. Mohamed M.M. Abdel-Latif Ph.D.
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  2. Henry Windle Ph.D.
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  3. Ana Terres Ph.D.
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  4. Déirdre Ní Eidhin Ph.D.
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  6. John V. Reynolds M.D.
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Correspondence to Mohamed M.M. Abdel-Latif Ph.D..

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Abdel-Latif, M.M., Windle, H., Terres, A. et al. Helicobacter pylori extract induces nuclear factorkappa b, activator protein-1, and cyclooxygenase-2 in esophageal epithelial cells. Journal of Gastrointestinal Surgery 10, 551–562 (2006). https://doi.org/10.1016/j.gassur.2005.09.003

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