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Role of MD-2 in Tool-like receptor 4-dependent signaling in Helicobacter-pylori-associated gastritis

Research Project

Project/Area Number 13670520
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionShimane Medical University

Principal Investigator

ISHIHARA Shunji  Shimane Medical University, Assistant Professor, 医学部, 講師 (80263531)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsTLR4 / MD-2 / H.pyvlori / ECL cell / Toll-like receptor / H.Pylori
Research Abstract

Helicobacter pylori (H. pylori) lipopolysccharide (LPS) is one of the major virulence factors in the induction of gastritis. LPS-dependent activation of gastric epithelial cells and infiltrating macrophages leads to secretion of several proinflammatory cytokines. However, little is known about the recognition system of H. pylori LPS in gastric mucosal cells. Recent studies have shown that LPS initiates signal transduction through toll-like receptor (TLR)-4, and this pathway is activated by MD-2. The aim of this study is to investigate TRL-4/MD-2 complex-specific recognition of H. pylori LPS in gastric mucosal cells. Gastric antral biopsy samples were taken from patients with and without H. pylori infection. Four gastric cancer cell lines (MKN-7, MKN-28, MKN-45 and AGS) were used for in vitro study. Expression of TLR-4 and MD-2 in gastric biopsy specimens and gastric cancer cell lines was examined by reverse-transcription polymerase chain reaction and western blot analysis. Localization of TLR-4 in histological sections was also evaluated by immunohistochemistry. Luciferase assay was performed for the assessment of H. pylori LPS-induced NF-kB activation in gastric epithelial cells and transient transfectants expressing TLR-4 and/or MD-2. TLR-4 was constitutively expressed in the stomach with and without H. pylori infection and localized in gastric epithelial cells and infiltrating mononuclear cells. However, the expression of MD-2 in H. pylori-positive subjects was higher than that in H. pylori-negative subjects. In vitro, all gastric epithelial cells expressed both TLR-4 and MD-2 and H. pylori LPS stimulated NF-kB activation in these cells. LPS responses in transfectant expressing both TLR-4 and MD-2 was significantly higher than that expressing only TLR-4. TLR-4/MD-2 complex is essential for the recognition of H. pylori LPS and MD-2 may regulate TLR-4-dependent signaling in the development of H. pylori-associated gastritis.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (67 results)

All Other

All Publications (67 results)

  • [Publications] Ortega CF, Ishihara S, et al.: "Strategic compartmentalization of toll-like receptor 4"J.Immunol. 170. 3977-3985 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hamamoto S, Fukuda R, et al.: "9-cis retinoic acid enhances the anti-viral"Journal of Laboratory and Clinical Medicine. 141. 58-66 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sato H, Kawashima K, et al.: "Lafutidine, a novel histamine H2-receptor antagonist"Journal of Laboratory and Clinical Medicine. 141. 102-105 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazumori H, Ishihara S, et al.: "Localization of Reg receptor in rat fundic mucosa"Journal of Laboratory and Clinical Medicine. 139. 101-108 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawashima K, Ishihara S, et al.: "Localization of calcitonin gene-related peptide receptors"Peptides. 23. 955-966 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takashima T, Adachi K, et al.: "Cardiovascular risk factors in subjects with Helicobacter"Helicobacter. 7. 86-90 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazumori H, Ishihara S, et al.: "Time course changes of ECL cell markers in acetic"Alimentary Pharmacology and Therapeutics. 16. 10-19 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Rumi MAK, Sato H, et al.: "Growth inhibition of esophageal squamous carcinoma"Journal of Laboratory and Clinical Medicine. 140. 17-26 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshino N, Adachi K, et al.: "H.pylori infection does not affect the serum level"American Journal of Gastroenterology. 97. 2927-2928 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kadowaki Y, Ishihara S: "REG protein is overexpressed in gastric cancer"REG protein is overexpressed in gastric cancer. 530. 59-64 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ortrga C, Ishihara S, et al.: "Hepatocyte growth factor expression in the"Digestive Diseases and Science. 47. 2275-2285 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kaji T, Ishihara S, et al.: "Adherence of Helicobacter pylori to gastric epithelial cells"Journal of Laboratory and Clinical Medicine. 139. 244-250 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ortega CF, Ishihara S, et al.: "Strategic compartmentalization of toll-like receptor 4"J.Immunol. 170. 3977-3985 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukuda R, Hamamoto N, et al.: "Gastrointestinal stromal tumor with a novel mutation of KIT"Internal Medicine. 40. 301-303 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawamura A, Adachi K, et al.: "Correlation between microsatellite instability and"Cancer. 91. 339-345 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kinoshita Y, Ishihara S: "What is the role of adrenomedullin and proadrenomedullin"Journal of Gastroenterology. 36. 62-64 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazumori H, Ishihara S, et al.: "Analysis of gastrin recptor gene expression in"FEBS LETTERS. 489. 208-214 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishihara S, Fukuda R, et al.: "T cell-mediated cytotoxicity via Fas/Fas ligand signaling"Helicobacter. 6. 283-293 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Adachi K, Ishihara S, et al.: "Efficacy of ecabet sodium for Helicobacter pylori"Alimentary Pharmacology and Therapeutics. 15. 1187-1191 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Rumi MAK, Sato H, et al.: "Peroxisome proliferator -activated receptor γ ligand"British Journal of Cancer. 84. 1640-1647 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishihara S, Okuyama T, et al.: "Intragastric distribution of Helicobacter pylori during"Alimentary Pharmacology and Therapeutics. 15. 1485-1491 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Moriyama N, Ishihara S, et al.: "E-Cadherin is essential for gastric epithelial"Journal of Laboratory and Clinical Medicine. 138. 236-242 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ortega CF, Ishihara S, et al.: "Strategic compartmentalization of toll-like receptor 4 in the mouse gut"J. Immunol.. 170. 3977-3985 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hamamoto S, Fukuda R, et al.: "9-cis retinoic acid enhances the anti-viral effect of interferonon hepatitis C virus replication through increased expression of type-I interferon receptor"Journal of Laboratory and Clinical Medicine. 141. 58-66 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sato H, Kawashima K,et al.: "Lafutidine, a novel histamine H2-receptor antagonist, increases serum calcitonin gene-related peptide in rats after water immersion-restraint stress"Journal of Laboratory and Clinical Medicine. 141. 102-105 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazumori H, Ishihara S, et al.: "Localization of Reg receptor in rat fundic mucosa"Journal of Laboratory and Clinical Medicine. 139. 101-108 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawashima K, Ishihara S, et al.: "Localization of calcitonin gene-related peptide receptors in rat gastric mucosa"Peptides. 23:5. 955-966 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takashima T, Adachi K, et al.: "Cardiovascular risk factors in subjects with Helicobacter pylori infection"Helicobacter. 7:2. 86-90 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazumori H, Ishihara S, et al.: "Time course changes of ECL cell markers in acetic acid-induced gastric ulcers in rats"Alimentary Pharmacology and Therapeutics. 16 suppl 2. 10-19 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazumori H, Ishihara S, et al.: "Time course changes of ECL cell markers in acetic acid-induced gastric ulcers in rats"Alimentary Pharmacology and Therapeutics. 16 suppl 2. 10-19 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yashino N, Adachi, et al.: "H.pylori infection does not affect the serum level of homocysteine"America Journal of Gastroenterolog. 97:11. 2927-2928 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kadowaki Y, Ishihara S et al.: "REG protein is ovwerexpressed in gastric cancer cells, where it activates a signal transduction pathway which converges an ERKI/2, and stimulates growth"FEBS LETTERS. 530. 59-64 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ortrga C, Ishihara S, et al.: "Hepatocyte growth factor expression in the regenerating colon after dextran sodium colitis in rats"Digestive Diseases and Science. 47:10. 2275-2285 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kaji.T, Ishihara S, et al.: "Adherence of Helicobacter pylori to gastric epithelial cells and mucosal inflammation"Journal of Laboratory and Clinical Medicine. 139. 244-250 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukuda R, Hamamoto N, et al.: "Gastrointestinal stromal tumor with a novel mutation of KIT proto-oncogene"Internal Medicine. 40. 301-303 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawamura A, Adachi K, et al.: "Correlation between microsatellite instability and metachronous disease recurrence after endoscopic mucosal resection in patients with early stage gastric carcinoma"Cancer. 91:2. 339-345 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kinoshita Y, Ishihara S.: "What is the role of adrenomedullin and proadrenomedullin N-terminal 2C peptide produced in the gastrointestinal tract?"Joumal of Gastroenterology. 36:1. 62-64 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazumori H, Ishihara S, et al.: "Analysis of gastrin receptor gene expression in proliferating cells in the neck zone of gastric fundic glands using laser capture microdissection"FEBS LETTERS. 489:2-3. 208-214 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishihara S, Fukuda R, et al.: "T cell-mediated cytotoxicity via Fas/Fas ligand signaling in Helicobacter pylori-infected gastric corpus"Helicobacter. 6:4. 283-293 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Adachi K, Ishihara S et al.: "Efficacy of ecabet sodium for Helicobacter pylori eradication triple therapy in comparison with a lansoprazole-based regimen"Alimentary Pharmacology and Therapeutics. 15:8. 1187-1191 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Rumi MAK, Sato H, et al.: "Peroxisome proliferator -activated receptor yligand induced growth inhibition of human hepatocellular carcinoma"British Joumal of Cancer. 84:12. 1640-1647 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishihara S. Okuyama T, et al.: "Intragastric distribution of Helicobacter pylori during short-term omeprazole therapy : study using Carnoy's fixation and immunohistochemistry for detection of bacteria"Alimentary Pharmacology and Therapeutics. 15:9. 1485-1491 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Moriyama N, Ishihara S, et al.: "E-Cadherin is essential for gastric epithelial restitution in vitro: a study using the normal rat gastric mucosal cell line, RGM1"Journal of Laboratory and Clinical Medicine. 138:4. 236-242 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okuyama T, et al.: "A novel doudenal elevated lesion mimicking intraluminal doudenal"Gastrointestinal Endoscopy. 55. 750-752 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kazumori H, et al.: "Localization of Reg receptor in rat fundic mucosa"J. Lab. Clin. Med. 139. 101-108 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takashima T, et al.: "Cardiovascular risk factors in subjects with Helicobacter pylori"Helicobacter. 7. 86-90 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawashima K, et al.: "Locolization of calcitonin gene-related peptide receptors in rat"Peptides. 23. 955-966 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kaji T, et al.: "Adherence of Helicobacter pylori to gastric epithelial"J. Lab. Clin. Med. 139. 244-250 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kazumori H, et al.: "Time course changes of ECL cell markers in acetic acid-induced"Alimentary pharmacology and Therapeutics. 16. 10-19 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sato H, et al.: "Primary hyperparathyroidism with duodenal ulcer and"Internal Medicine. 41. 377-380 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Rumi Mak, et al.: "Growth inhibition of esophageal squamous carcinoma cells"J. Lab. Clin med. 140. 17-26 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Adachi K, et al.: "Comparative evaluation of urine-based and other minimally invasive"J. Gastroenterology. 37. 703-708 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sato H, et al.: "Successful endoscopic injection sclerotherapy for duodenal"J. Gastroenterology. 37. 143-144 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawamura A, et al.: "Helicobacter pylori-independent effect of hyperglycemia on gastric"Am. J. Gastroenterol. 97. 2479-2480 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okuyama T, et al.: "Activation of prostaglandin E2 receptor"J. Lab. Clin. Med. 140. 92-102 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okuyama T, et al.: "Angiolipoma of the colon diagnosed after endoscopic"Gastrointest Endosc. 55. 748-750 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshino N, et al.: "Helicobacter pylori infection does not affect the serum"Am J Gastroenterol. 97. 2979-2928 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ortaga-Cava CE, et al.: "Hepatocyte growth factor expression in dextran sodium"Dig. Dis. Sci. 47. 2275-2285 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kadowaki Y, et al.: "Reg protein is overexpressed in gastric cancer cells"FEBS Lett.. 530. 59-64 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sato H, et al.: "Lafutidine pretreatment causes increase in serum"J. Lab. Clin. Med. 141. 102-105 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujishiro H, et al.: "Analysis of urgent colonoscopy for acute lower intestinal"Digestive Endoscopy. 15. 117-120 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takashima T, et al.: "Cardiovascular risk factors in subjects with Helicobacter pylori"Helicobacter. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Kazumori H, et al.: "Localization of Reg receptor in rat fundic mucosa"Journal of Laboratory and Clinical Medicine. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujishiro H, et al.: "Influence of Helicobacter pylori infection on the prevalence of reflux"Journal of Gastroenterology and Hepatology. 16. 1217-1221 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Adachi K, et al.: "Influence of Helicobacter pylori infection and cetraxate on gastric"Journal of Gastroenterology and Hepatology. 16. 1211-1216 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishihara S, et al.: "T cell-mediated cytotoxicity via Fas/Fas ligand signaling in Helicobacter"Helicobacter. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishihara S, et al.: "Intragastric distribution of Helicobacter pylori during short-term"Alimentary Pharmacology and Therapeutics. 15. 1485-1491 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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