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Role of NF-kappaB in the growth, differentiation and apoptosis of gastric epithelial cells

Research Project

Project/Area Number 13670515
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MIYAZAKI Yoshiji  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30303960)

Co-Investigator(Kenkyū-buntansha) KIYOHARA Tatsuya  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (50322178)
SHINOMURA Yasuhisa  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90162619)
北村 信次  大阪大学, 医学部・附属病院, 医員
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsNF-kappaB / H-pylori / gastrin / gastric epithelial cells / IKK / protein kinase C / NIK / TRAF6
Research Abstract

We have shown that enlarged fold gastritis with H. pylori infection is characterized by marked infiltrates of macrophages and polynuclear cells, high production of interleukin-1 beta and hypergastrinemia. The present study was performed to investigate the effects of gastrin on activation of NF-kappaB in gastric epithelial cells. For this purpose, we created a cell line stably expressing gastrin receptor by introducing gastrin receptor cDNA into MKN28 gastric cancer cells. Using this cell line and isolated guinea-pig gastric epithelial cells, we obtained the following results. 1. Gastrin activates NF-kappaB, which was inhibited by protein kinase C (PKC) inhibitors. 2. Introduction of dominant negative IKK, NIK, or TRAF6 inhibited gastrin-induced activation of NF-kappa. 3. Inhibition of PKC-delta by eitherrottlerin or dominant negative PKC-delta inhibited gastrin-induced activation of NF-kappa 4.Gastrin activates PKC-delta in gastric epithelial cells within 5 minutes and this effect persisted for over 60 minutes. 5. Introduction of PKC-delta cDNA into gastric epithelial cells alone was able to activate NF-kappaB and this effect was inhibited by cotransfection of dominant negative IKK, NIK, or TRAF6. The data presented here suggest that gastsin promotes gastric inflammation through activation of NF-kappaB.

Report

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

    (24 results)

All Other

All Publications (24 results)

  • [Publications] M.Toyota, et al.: "Gastrin activates NF-κB through a protein kinase C-dependent pathway involving NF-κB-inducing kinase, IκB kinase and TRAF6 in MKN-28 cells transfected with gastrin receptor"Gut. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Toyota, et al.: "Peroxisome proliferator-activated receptor γ reduces the growth rate of pancreatic cencer cells through the reduction of cvclin D1"Life Sci. 121(1). 1565-1575 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] R.Takakura, et al.: "Enhanced macrophage responsiveness to lipopolysaccharide and CD40 stimulation in a murine model of inflammatory bowel disease : IL-10-deficient mice"Inflamm Res. 51(8). 409-415 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Nakahara et al.: "Deficiency of KIT-positive cells in the colon of patients with diabetes mellitus"J Gastroenterol Hepatol. 17(6). 666-670 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Ichiba, et al.: "Epidermal growth factor inhibits the growth of TE8 esophageal cancer cells through the activation of STAT1"J Gastroenterol. 37(7). 497-503 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Murayama, et al.: "Significance of the association between heparin-binding epidermal growth factor-like growth factor and CD9 in human gastric cancer"Int J Cancer. 98(4). 505-513 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toyota M, et al.: "Peroxisome proliferator-activated receptor gamma reduce, the growth rate of pancreatic cancer cells through the reduction of cyclin D1"Life Sci.. 70(13). 1565-1575 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takakura R, et al.: "Enhanced macrophage responsiveness tolipopolysaccharide and CD40 stimulation in amurine model of inflammatory bowel disease: IL-10-deficient mice"Inflamm Res.. 51(8). 409-415 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murayama Y, et al.: "Significance of the association between heparin-binding epidermal growth factor-like growth factor and CD9 in human gastric cancer"Int J Cancer. 98(4). 505-513 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ichiba M, et al.: "Epidermal growth factor inhibits the growth of TE8 esophageal cancer cells through the activation of STAT1"J Gastroenterol.. 37(7). 497-503 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakahara M, et al.: "Deficiency of KIT-positive cells in the colon of patients with diabetes mellitus"J Gastroenterol Hepatol.. 17(6). 666-670 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toyota M, et al.: "Gastrin activates NF-kB through a protein kinase C-dependent pathway involving NF-kB-inducing kinase, IkB kinase and TRAF6 in MKN-28 cellstransfected with gastrin receptor"Gut. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Toyota, et al.: "Gastrin activate NF-κB through a protein kinase C-dependent pathway involving NF-κB-inducting kinase, IκB kinase and TRAF6 in MKN-28 cells transfected with gastrin receptor"Gut. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Toyota, et al.: "Peroxisome proliferator-activated receptor γ reduces the growth rate of pancreatic cencer cells through the reduction of cyclin D1"Life Sci. 121(1). 1565-1575 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] R.Takakura, et al.: "Enhanced macrophage responsiveness to lipopolysaccharide and CD40 stimulation in a murine model of inflammatory bowl disease : IL-10-deficient mice"Inflamm Res. 51(8). 409-415 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Nakahara, et al.: "Deficiency of KIT-positivecells in the colon of patients with diabetes mellitus"J Gastroenterol Hepatol. 17(6). 660-670 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Ichiba, et al.: "Epidermal growth factor inhibits the growth of TE8 esophageal cancer cells through the activation of STAT1"J Gastroenterol. 37(7). 497-503 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Murayama, et al.: "Significance of the association between heparin-binding epidermal growth factor-like growth factor and CD9 in human gastric cancer"Int J Cancer. 98(4). 505-513 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Toyama, et al.: "Peroxisome proliferator-activated receptor γ reduces the growth rate of pancreatic cencer cells though the reduction of cyclin D1"Life Sci. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Miyazaki, et al.: "Epidermal growth factor receptor mediates stress-induced expression of its ligands in rat gastric epithelial cells"Gastroenterology. 121(1). 108-116 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Hiraoka, et al.: "Gastrin induces CXC chemokine expression in gastric epithelial cells though activation of NF-kappaB"Am J Physiol. 281(3). G735-G742 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Kitamura, et al.: "PPARγ agonists inhibit cell growth and suppress the expression of cyclin D1 and EGF-like growth factors in ras-transformed rat intestinal epithelial cells"Int. J. Cancer. 94(3). 335-342 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 北村信次, 他: "PPARγと大腸癌"早期大腸癌. 5(3). 283-286 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 宮崎義司, 他: "大腸癌とPPARγ"G. I. Research. 9(5). 415-420 (2001)

    • Related Report
      2001 Annual Research Report

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

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