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1998 Fiscal Year Final Research Report Summary

Role of Helicobacter pylori cytotoxin in the gastric mucosa

Research Project

Project/Area Number 08670611
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionOsaka City University

Principal Investigator

ARAKAWA Tetsuo  Osaka City University, Medical School, Associate Professor, 医学部, 助教授 (60145779)

Co-Investigator(Kenkyū-buntansha) FUJIWARA Yasuhiro  Osaka City University, Medical School, Research Associate, 医学部, 助手 (40285292)
HIGUCHI Kazuhide  Osaka City University, Medical School, Lecture, 医学部, 講師 (20218697)
Project Period (FY) 1996 – 1998
KeywordsHelicobacter pylori / cytotoxin / gastric mucosa / inflammatory cytokine / interleukin-1beta / cell proliferation / epidermal growth factor / neutrophil
Research Abstract

Helicobacter pylori infection in the gastric mucosa is strongly associated with chronic type B gastritis and peptic ulcer disease. However the pathogenic mechanisms of the H.pylori related disease is not known. Cytotoxin, which is produced by H.pylori and induces vacuolization in the target cells, is one of the major causative factors. In this research project, we focused on the role of the H.pylori cytotoxin in the gastric mucosa and examined whether H.pylori cytotoxin affects proliferation of the gastric cells and inflammatory cytokine production such as interleukin-1 beta (IL-1beta) and tumor necrosis factor- alpha (TNF- alpha) by human monocytes. We found that 1) H.pylori cytotoxin inhibited growth and proliferation of phuman gastric cultured cells and interferes with epidermal growth factor (EGF) binding to its receptor on the cell surface. 2) H.pylori stimulated inflammatory cytokine production and expression of messenger RNA by human isolated monocytes. 3) Prostaglandin E_2, which plays a central role in the gastric mucosal defense, inhibited H.pylori-induced inflammatory production by human monocytes. 4) These inflammatory cytokine induced gastric ulcer recurrence through increased expression of adhesion molecules and neutrophil infiltration in the rat experimental models and induced MCP-1 expression at the ulcer margin. 5) Interleukin-8 which is high concentration in the H.pylori infected gastric mucosa stimulated intraepithelial margination of neutrophils and impaired epithelial barrier function in the in vitro models. 6) Immunohistochemical study using human biopsy specimens of the H.pylori infected mucosa showed increased expression of ICAM-1, LFA-1, and Mac-1 in the gastric mucosa. These findings contributes pathogenesis of H.pylori related disease and the role of H.pylori cytotoxin in the gastric mucosa.

  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Arakawa T.: "Vlor Recunence:cytokines and inflammatory response-dependert drocess" Dig Dis Su. 43. 61-66 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Higuchi K.: "In situ expressin of cell adhesion nolocules in chromic gostritis with Helicobacter pylori infection" J Clin Gastrocutrl. 25. 215-221 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujiwara Y.: "Helicobacter pylori cultare supeunataut inhibits binding and drolilactive response of hawau gosfr cells to EGF" Digestion. 58. 299-303 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tominaga K.: "Incveased in RNA levels of TNF-1 and MCP-l in wa relapse caused by 1L-1β" Dig Dis Su. 43. 134-138 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe T.: "Role of neutrophils in a rat modcl of gastrs ulce rewnence caused by inter Eukin-1β" Am J Pathol. 150. 971-979 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujiwara Y.: "Interlcukin-8 stivulates leukoate. migration across a monolayer of cultured gastuc epithelid cells." Dig Dis Su. 42. 1210-1215 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Arakawa T: "Bioreyulatin and its disorder in the gcstrointestual tract" Blackwell saence Japan, 374 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Arakawa T.: "Ulcer recurrence : cytokines and inflammatory response-dependent process" Dig Dis Sci. 43. 61-66 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Higuchi K.: "In situ expression of cell adhesion molecules in chronic gastritis with Helicobacter pylori infection." J Clin Gastroenterol. 25 (suppl 1). S215-221 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujiwara Y.: "Helicobacter pylori culture supernatant inhibits binding and proliferative response of human gastric cells to epidermal growth factor : implications for H.phlori interference with ulcer healing?" Digestion. 58. 299-303 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujiwara Y.: "Interleukin-8 stimulates leukocyte migration across a monolayer of cultured rabbit gastric epithelial cells : effect associated with the impairment of gastric epithelial barrier function." Dig Dis Sci. 42. 1210-1215 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tominaga K.: "Increased mRNA levels of transforming growth factor-beta1 and monocyte chemoattractant protein-1 in ulcer relapse caused by interleukin-1beta in rats." Dig Dis Sci. 43 (suppl). 134-138 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe T.: "Role of neutrophils in a rat model of gastric ulcer recurrence caused by interleukin-1beta" Am J Pathol. 150. 971-979 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Arakawa T.: "Helicobacter phlori in peptic ulcer disease : A monster ort a ghost. Yoshikawa T and Arakawa T eds.Bioregulation and its disorder in the gastrointestinal tract." Blackwell Science Japan. 177-183 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Higuchi K.: "Helicobacter pylori and quality of ulcer healing. Yoshikawa T and Arakawa T eds.Bioregulation and its disorder in the gastrointestinal tract." Blackwell Science Japan. 185-192 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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