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1997 Fiscal Year Final Research Report Summary

Pathophysiological and pharmacological studies on chemokines

Research Project

Project/Area Number 08044263
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field Immunology
Research InstitutionUniversity of Tokyo

Principal Investigator

MATSUSHIMA Kouji  University of Tokyo, Graduate School of Medicine, Department of Moleclar Preventive Medicine, Professor, 大学院医学系研究科, 教授 (50222427)

Co-Investigator(Kenkyū-buntansha) OPPENHEIM Joost.J.  National Cancer Institute (USA), Laboratory of Molecular Immunoregulation, Chief, 研究室主任
HARADA Akihisa  Kanazawa University, School of Medicine, Department of Hygiene, Research Associa, 医学部, 助手 (00228636)
KOBAYASHI Yoshiro  Toho University, Faculty of Science, Professor, 理学部, 教授 (10134610)
KASAHARA Tadashi  Koristu College of Pharmacy, Division of Biochemistry, Professor, 薬学部, 教授 (60049096)
MUKAIDA Naofumi  Kanazawa University, Cancer Research Institute, Department of Molecular Pharmaco, がん研究所, 助教授 (30182067)
Project Period (FY) 1996 – 1997
KeywordsChemokine / interleukin-8 / MCAF / MCP-1 / neutrophils / monocytes / inflammation / HIV infection / receptor
Research Abstract

This study was performed to develop novel types of anti-inflammatory and immunoregulatory agents through elucidating the pathophysiological roles of chemokines including interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF/MCP-1). Through these studies, we obtained the results as follows.
#1.In collaboration with Dr.Thestrup-Pedersen's group, we observed that IL-8 recetor expression on B cells was up-regulated in HIV-infected asymptomatic patients, compared with normal persons. Moreover, we observed that B cells from HIV-infeced patients responded differentially to various Th1 and Th2 cytokines, in terms of IL-8 receptor expression.
#2.In collaboration with Dr.Thestrup-Pedersen's group, we demonstrated that plasma IL-8 levels elevated immediately after the liver transplantation, probably reflecting reperfusion injury to transplanted organs.
#3.In collaboration with Dr.Oppenheim'sgroup, we demonstrated that IL-8 induced the phosphorylation of CXCR2 (IL-8 receptor type B) more strongly, than NAP-2. Moreover, we revealed the strong phosphorylation resulted in reduced neutrophil chemotactic activity in response to high concentrations of IL-8.
#4.In collaboration with Dr.Oppenheim, we established a sensitive enzyme-linked immunosorbent assay for a CC hemokine, eotaxin.
#5.We established the essential involvement of IL-8 in neutrophil-mediated tissue injuries, such as acute respiratory distress syndrome and brain reperfusion injury model of rabbit. Moreover, we revealed that MCAF/MCP-1 was crucially involved in anti-glomerular basement membrane antisera-induced crescentic shronic glomerulonephritis model.
#6.We demonstrated that cytomegalovirus induced IL-8 production in vitro and that IL-8 attenuated anti-viral activities of interferon.
The discussion with Drs.Thestrup-Pedersen and Oppenheim has given us invaluable advice when performing studies #5 and #6.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Wada.T.,et.al.: "Intervention of croscentic glomerulonephritis in rats by administering antibodies against monocyte chemetactic and activating factor(MCAF)." FASEB J.10. 1418-1425 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Gesser,B.,et.al.: "IL 8 induces T cell chemotaxiz,suppresses IL 4,and up-regulates IL 8 production by CD4+ Tcells." J.Leukoc.Biol.59. 407-411 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Jinquan,T.,et.al.: "Chemotaxis and IL-8 receptor expression in B cells from normal and HIV-infected subjects." J.Immunol.158. 475-484 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ben-Baruch,A.,et.al.: "The differential ability of IL-3 and neutrophil activating peptide-2 to induce attenuation of chemctaxis is mediated by their divergent capabilities to phosphorylate CXCR2(IL-8 receptor B)." J.Immunol.158. 5927-5933 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sonoda,Y.,et.al.: "Stimulation of IL-8 production by okadaic acid and vanadare in a human promyelocytic cell line,HL-60 subline:Possible role of MAP kinase in okadaic acid-induced NF-kB activation." J.Biol.Chem. 27. 15366-15372 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Khabar,K.S.A.,et.al.: "The α-chemokine,interleukin-8,inhibits the antiviral action of interferon α." J.Exp.Med.186. 1077-1085 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Harada,A.,Mukaida,N.,and Matsushima,K.: "The role of chemokines in ischemia and reperfusion injury." R.G.Landers Company, 14 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Harada,A.,Mukaida,N.,and Matsushima,K.: "The biological biochemical and molecular profile of leukocyte chemotactic and activating cytokine,interleukin-8." JAI Press, 39 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wada, T., Yokoyama, H., Furuichi, K., Kobayashi, K.-i., Harada, K., Naruto, M., Su, S.-b., Akiyama, M., Mukaida, N., and Natsushima, K.: "Intervention of crescentic glomerulonephritis in rats by administering antibodies against monocyte chemotactic and activating factor (MCAF)." FASEB,J.10. 1418-1425 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Gesser.B., Lund, M., Loshe, N., Vestergaad, C., Matsushima, K., Sindet, Pedersen, S., Jensen, S.L., Thestrup-Pedersen, K,and Larsen, C.G.: "IL 8 induces T cell chemotaxiz, suppresses IL 4, and up-regulates IL 8 production by CD4+ Tcells." J.Leukocyte.Biol.59. 407-411 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jinquan, T., Moller, B., Storgaard, M., Mukaida, N., Bonde, J., Grunnet, J., Black, F.T., Larsen, C.G., Matsushima, K., and Thestrup-pedersen, K.: "Chmtaxis and IL-8 receptor expression in B cells from normal and HIV-infected subjects." J,Immunol.158. 475-484 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ben-Baruch, A., Grimm, M., Bengali, K., Evans, G.A., Chertov, O., Wang, J.M., Howard, Z., Mukaida, N., Matsushima, K., and Oppenheim, J.J.: "The differential ability of IL-8 and neutrophil activating peptid-2 to induce attenuation of chemotaxis is mediated by their divergent capabilities to phosphorylate CXCR2 (IL-8 receptor B)." J.Immunol.158. 5927-5933 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sonoda, Y., Kasahara, T., Yamaguchi, Y., Kuno, K., Matsushima, K., and Mukaida, N.: "Stimulation of IL-8 production by okadaic acid and vanadate in a human promylocytic cell line, HL-60 subline : Possible role of MAP kinase in okadaic acid-induced NF-xB activation." J.Biol.Chem.27. 15366-15372 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Khadar, K.S.A., Al-Zoghaibi, Al-Ahdal, M.N., F., Murayama, T., Dhalla, M., Mukaida, N., Taha, M., Al-Sedairy, S.T., Siddiqui, Y.M., Kessie, G., and Matsushima, K.: "The alpha-Chemokine, interleukin-8, inhibits the antiviral action of interferon alpha." J.Exp.Med.186. 1077-1085 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Harada, A., Mukaida, N., and Matsushima, K.: The role of chemokines in ischemia and reperfusion injury.R.G.Landers Company, 14 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Harada, A., Mukaida, N., and Matsushima, K.: The biological, biochemical and molecular profile of leukocyte chemotactic and activating cytokine, interleukin-8.JaI Press, 39 (1997)

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

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Published: 1999-03-16  

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