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2001 Fiscal Year Final Research Report Summary

Development of assay systems for chemokines and their receptors and establishment of their diagnostic value

Research Project

Project/Area Number 10557249
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Laboratory medicine
Research InstitutionKanazawa University

Principal Investigator

MUKAIDA Naofumi  Kanazawa University, Cancer Research Institute, Professor, がん研究所, 教授 (30182067)

Project Period (FY) 1998 – 2001
Keywordsinterleukin-8 (IL-8) / MGP-1 / angiogenesis / hypoxia / MIP-lα / hepatitis C virus / CCR1 / NF-_kB
Research Abstract

1) A functional interleukin-8 (IL-8) homologue, macrophage inflammatory protein (MIP)-2, was produced by mouse vaginal epithelium, periodically after ovulation and caused neutrophil infiltration into vaginal epithelium.
2) In acute type of IgA nephropathy, urinary IL-8 levels were increased with undetectable urinary monocyte chemoattractant protein (MCP)-1. In contrast, MCP-1 but not IL-8 levels were increased in urines from chronic type of IgA nephropathy patients. Moreover, crescentic glomerulonephritis, MIP-lα and MCP-1 produced in the kidney, were responsible for crescent formation and interstitial lesions, respectively. Furthermore, in diabetic nephropathy, macrophages in interstitium were positive for MCP-1 and urinary MCP-1 levels were increased.
3) IL-8 protein and mRNA were detected near necrotic areas inside tumor tissues, where oxygen content is presumed to be low. The exposure of several types of cell lines to hypoxia activated two transcription factors, NF-_kB and AP-1, and eventually induced IL-8 gene transcription. Human gastric cancer cell lines transfected with IL-8 gene exhibited faster tumor formation with enhanced angiogenesis when injected into nude mice, compared with parental cells. Moreover, most of gastric cancer cell lines expressed IL-8 receptors and IL-8 induced the expression of metastasis-related genes in some gastric cancer cell lines.
4) In hepatoma cell lines, two distinct transcription factors, PEA3 and AP-1, were constitutively activated, which resulted in constitutive IL-8 gene transcription. Among patients infected with human hepatitis C virus, serum IL-8 levels were increased in patients suffering from hepatoma, when compared with chronic hepatits and liver cirrhosis patients. Moreover, the transduction of nonstructural protein (NS) 5A of human hepatitis C virus induced IL-8 gene transcription as well as IL-8 protein secretion.
5) In cord blood, CCR1 expression among CD34-positive cells, was restricted to erythroid progenitor cells.

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Sonoda, Y., Mukaida, N., Wang, J.-b.Shimada, Hiratsuka, M., Naito, M., Kasahara, T., Harada, A., Inoue, M., Matsushima, K.: "Physiologic regulation of postovulatory neutrophil migration into vagina by a C-XC chemokine(s)"Journal of Immunology. 160. 6159-6165 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wada, T., Furuichi, K., Segawa, C., Shimizu, M., Sakai, N., Takeda, S., Takasawa, K., Kido, H., Kobayashi, K., Mukaida, N., Ohmoto, Y., Matsushima, K., Yokoyama, H.: "MIP-1α and MCP-1 contribute to crescents and interstitial lesions via the cognate chemokine receptor in human crescentic glomerulonephritis"Kidney International. 56. 995-1003 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Xu, L., Xie, K., Mukaida, N., Matsushima, K., Fidler, I.J.: "Hypoxia-induced elevation in interleukin-8 expression by human ovarian cancer carcinoma cells"Cancer Res.. 59. 5822-5829 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iguchi, A., Kitajima, I., Yamakuchi, M., Ueno, S., Aikou, T., Kubo, T., Matsushima, K., Mukaida, N., Maruyama, I.: "PEA3 and AP-1 are required for constitutive IL-8 gene expression in hepatoma cells"Biochem. Biophys, Res. Commun.. 279. 166-171 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Polyak, S.J., Khabar, K.S.A., Paschal, D.M., Ezelle, H.J., Duverlei, G., Barber, G.N., Levy, D.E., Mukaida, N., Gretch, D.R.: "Hepatitis C virus nonstructural 5A protein induces interleukin-8, leading, to partial inhibition of the interferon-induced antiviral response"Journal of Virology. 75. 6095-6106 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] de Wynter, E.A., Heyworth, C.M., Mukaida, N., Jaworska, E., Weffort-Santos, A., Matsushima, K., Testa, N.G.: "CCR1 chemokine receptor expression isolates erythroid from granulocyte-macrophage progenitors"Journal of Leukocyte Biology. 70. 455-460 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 向田 直史: "標準薬理学(第6版)"医学書院. 15/477 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sonoda, Y, Mukaida. N. Wang, J.-b., Shimada-Hiratsuka, M., Naito, M., Kasahara, T., Harada, A., Inoue, M., Matsushima, K: "Physiologic regulation of postovulatory neutrophil migration into vagina by a C-X-C chemokine(s)."Journal of Immmunology. 160. 6159-6165 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wada, T., Furuichi, K, Segawa, G, Shimizu, M., Sakai, N., Takeda, S.I., Takasawa, K, Kida, H., Kobayashi, K.-I., Mukaida. N. Ohmoto, Y., Matsushima, K, and Yokoyama, H: "MIP-1αand MCP-1 contribute to crescents and interstitial lesions via the cognate chemokine receptor in human crescentic glomerulonephritis"Kidney International. 56. 995-1003 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Xu, L., Xie, K, Mukaida. N. Matsushima, K, and Fidler, I.J.: "Hypoxia-induced elevation in interleukin-8 expression by human ovarian cancer carcinoma cells"Cancer Research. 59. 5822-5829 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iguchi, A., Kitajima, L, Yamakuchi, M., Ueno, S., Aikou, T., Kubo, T., Matsushima, K, Mukaida. N., Maruyama, I: "PEA3 and AP-1 are required for constitutive IL-8 gene expression in hepatoma cells"Biochemical and Biophysical Research Communication. 279. 166-171 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Polyak,S. J., Khabar, K.SA, Paschal, D.M., Ezelle, H.J., Duverlei, G., Barber, G.N., Levy, D.E., Mukaida. N., Gretch, DH.: "Hepatitis C virus nonstructural 5A protein induces interleukin-8, leading to partial inhibition of the interferon-induced antiviral response"Journal of Virology. 75. 6095-6106 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] de Wynter, E.A., Heyworth, CM., Mukaida. N. Jaworska, E., Weffort-Santos, A., Matsushima, K, Testa, N.G: "CCRl chemokine receptor expression isolates erythroid from granulocyte-macrophage progenitors"Journal of Leukocyte Biology. 70. 455-460 (2001)

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

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Published: 2003-09-17  

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