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Suppression of hepatocyte growth factor induction by interleukin 1 and its role in the termination of liver regeneration

Research Project

Project/Area Number 13672285
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionOKAYAMA UNIVERSITY

Principal Investigator

GOHDA Eiichi  Okayama University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (20028814)

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: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsHepatocyte growth factor (HGF) / Interleukin 1(IL-1) / Tumor necrosis factor α (TNF-α) / Cyclic AMP / Cholera toxin / Phorbol ester / Epidermal growth factor (EGF) / インターロイキン1(IL-1) / tumor necrosis factor α(TNF-α) / MAPキナーゼ
Research Abstract

HGF production in cultured human dermal fibroblasts is induced by PKA-activating agents such as 8-bromo-cAMP and cholera toxin, phorbol esters such as TPA, and growth factors such as EGF. HGF production in various types of cells is also stimulated by IL-1 and TNF-α. When we examined combined effects of HGF inducers, we unexpectedly found that IL-1 strongly inhibited the induction of HGF. In this study, this inhibition was characterized. HGF production in human dermal fibroblasts was induced only slightly by IL-1 α IL-1 β and TNF-α. However, IL-1 α, IL-1β and TNF-α strongly inhibited 8-bromo-cAMP- and cholera toxin-induced HGF production. Maximal inhibitions by IL-1 and TNF-α were observed at 100 pg/mL and 3 JRU/mL, respectively. The inhibitory effects of IL-1 and TNF-α were larger than that of dexamethasone and were as large as or larger than that of TGF-β. The inhibitory effects of IL-1 and TNF-α were detected at and offer 48 h of incubation. Results of Northern blot analysis showed t … More hat both IL-1 and TNF-α inhibited the up-regulation of HGF gene expression induced by cholera toxin. The inhibitory effect of IL-1 was diminished by the IL-1 receptor antagonist. HGF inductions by EGF and TPA were also suppressed by IL-1. The inhibitory effect of IL-1 on EGF-induced HGF production was smaller than that of TGF-β but larger than those of dexamethasone and rethoic acid. The signal of IL-1 is transmitted through the MAPK family cascade and the IKK cascade. The inhibitory effect of IL-1 was not diminished by NF-kB inhibitors but diminished partially by the inhibitor of either p38 or MEK and significantly by the combination of both inhibitors, suggesting that the activation of p38 and MEK-MAPK but not the activation of NF-kB is at least partly involved in the inhibitory effect of IL-1. Since IL-1 inhibits DNA synthesis in adult rat hepatocytes in primary culture, it is possible that IL-1 acts as a dual inhibitor of DNA synthesis in liver regeneration: it not only directly inhibits DNA synthesis of hepatocytes, but also suppresses production of HGF. Less

Report

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

    (6 results)

All Other

All Publications (6 results)

  • [Publications] 合田榮一: "肝細胞増殖因子(HGF)の機能と産生制御"日本薬理学雑誌. 119巻5号. 287-294 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ejichi Gohda: "Suppression of hepatocyte growth factor induction in human dermal fibroblasts by tumor necrosis factor-α"Proceedings of the Third International Symposium on Recent Advances in Inflammation Research(Kyongsan, Korea). 53-55 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Eiichi Gohda: "Function and regulation of production of hepatocyte growth factor (HGF)"Folia Phaimacol. Jpn. (Nippon Yakurigaku Zasshi). 119(5). 287-294 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Eiichi Gohda: "Suppression of hepotocyte growth factor induction in human dermal fibroblasts by tumor necrosis factor-α"Proceedings of the Third International Symposium on Recent Advances in Inflammation Research. (Kyongsan,Korea). 53-55 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Eiichi Gohda: "Suppression of hepatocyte growth factor induction in human dermal fibroblasts by tumor necrosis factor-α"Proceedings of the Third International Symposium on Recent Advances in Inflammation Research (Kyongsan, Korea). 53-55 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 合田榮一: "肝細胞増殖因子(HGF)の機能と産生制御"日本薬理学雑誌. 119巻5号(掲載予定). (2002)

    • Related Report
      2001 Annual Research Report

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

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