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Expression of CXC chemokines lacking ELR-motif in liver diseases and its clinical significance

Research Project

Project/Area Number 10670494
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKyoto Prefectural University of Medicune

Principal Investigator

ITOH Yoshito  Kyoto Prefectural University of Medicine, Research Associate, 医学部, 助手 (70244613)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsCXC chemokine / ELR-motif / liver disease
Research Abstract

Human Studies:
The serum levels of interferon inducible protein 10 (IP-10) were elevated in patients with chronic liver diseases in proportion to the hepatic inflammation as assessed by serum AST and ALT, irrespective of the etiology. The serum levels of IP-10 also correlated well with the histological activity of hepatitis. The mRNA expression of IP-10 was observed in the hepatocytes in hepatic lobules which were surrounded by infiltrating lymphocytes not only in viral hepatitis but also in autoimmune hepatitis. We could not make a stable ELISA system for human Mig and we could not confirm the positive signal of Mig in human liver tissues.
We also measured the serum levels of IP-10 in patients with hepatocellular carcinoma (HCC). Although the serum levels of IP-10 in HCC were increased in HCC patients, the levels of IP-10 did not show a significant correlation with the tumor sizes nor the levels of serum tumor markers. The decompensated HCC patients or HCC patients with higher hepatic inflammatory activity tended to show higher levels of serum IP-10.
Animal Studies:
We made a ELISA systems of murine IP-10 and Mig which can evaluate the levels of these two chemokines. In control untreated mice, the chemokines were lower than the limits of detection. In experimental models of mouse liver injury, the serum levels of these chemokines increased as the progress of liver injury as assesses by the serum levels of AST and ALT.
By Northern blotting study, the mRNA of IP-10 and Mig was detected in the liver preceding the onset of hepatic inflammation. The in situ hybridization revealed that both hepatocytes and hepatic sinusoidal cells expressed the mRNA of these two chemokines.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Nishioji K: "Increase of chemokine interferon-inducible protein-10 (IP-10) in the serum of patients with autoimmune liver diseases and increase of its mRNA expression in hepatocytes."Clin Exp Immunol. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itoh Y: "Chemotactic cytokines (chemokines) in human hepatitis and experimental hepatitis models: which ones play the crucial role?"J Gastroenterol. 35. 724-725 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Narumi S: "TNF-α is a potent inducer for LEN-inducible protein-10 in hepatocytes and unaffected by GM-GSF in vivo, in contrast to IL-1β and IFN-γ."Cytokine. 12. 1007-1016 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tamani M: "Liver-Infiltrating Tlymphocytes are attracted selectively by LEN-inducible protein-10."Cytokine. 12. 299-308 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishioji K: "Experimental liver injury induced by Propionibacterium acnes and Lipopolysaccharide in macrophage colony stimulating factor-deficient osteopetrotic (op/op) mice."Dig Dis Sci. 44. 1975-1984 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itoh Y: "Serum levels of soluble tumor necrosis factor receptors and effects of interferon therapy in patients with chronic hepatitis C virus infection."Am J Gastroenterol. 94. 1332-1340 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itoh Y: "Hepatic damage induced by transcatheter arterial chemoembolization elevates serum concentrations of macrophage-colony stimulating factor."Liver. 19. 97-103 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K Nishioji, et al.: "Increase of chemokine interferon-inducible protein-10 (IP-10) in the serum of patients with autoimmune liver diseases and increase of its mRNA expression in hepatocytes."Clin Exp Immunol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y Itoh, et al.: "Chemotactic cytokines (chemokines) in human hepatitis and experimental hepatitis models : which ones play the crucial role?"J Gastroenterol. 35. 724-725 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S Narumi, et al.: "TNF-α is a potent inducer for IFN-inducible protein-10 in hepatocytes and unaffected by GM-GSF in vivo, in contrast to IL-1β and IFN-γ."Cytokine. 12. 1007-1016 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tamaru M, et al.: "Liver-Infiltrating T lymphocytes are attracted selectively by IFN-inducible protein-10."Cytokine. 12. 299-308 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishioji K, et al.: "Experimental liver injury induced by Propionibacterium acnes and Lipopolysaccharide in macrophage colony stimulating factor-deficient osteopetrotic (op/op) mice."Dig Dis Sci. 44. 1975-1984 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itoh Y, et al.: "Serum levels of soluble tumor necrosis factor receptors and effects of interferon therapy in patients with chronic hepatitis C virus infection."Am J Gastroenterol. 94. 1332-1340 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itoh Y, et al.: "Hepatic damage induced by transcatheter arterial chemoembolization elevates serum concentrations of macrophage-colony stimulating factor."Liver. 19. 97-103 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary

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Published: 1998-04-01   Modified: 2016-04-21  

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