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Analysis of the dynamic significance of IL-18 in allergic Patients

Research Project

Project/Area Number 12670446
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionHYOGO COLLEGE OF MEDICINE

Principal Investigator

YOSHIMOTO Tomohiro  Hyogo College of Medicine, Associate Professor, 医学部, 助教授 (60241171)

Co-Investigator(Kenkyū-buntansha) TUTUI Hiroko  Hyogo College of Medicine, Associate Professor, 医学部, 助教授 (40236914)
OKAMURA Haruki  Hyogo College of Medicine, Professor, 医学部, 教授 (60111043)
NAKANISHI Kenji  Hyogo College of Medicine, Professor, 医学部, 教授 (60172350)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsアレルギー / IL-18 / IgE / caspase-1 / アトピー性皮膚 / アトピー性皮膚炎
Research Abstract

IL-18, an IL-1-like cytokine that requires cleavage with caspase-1 to become actiye, has strong ability to induce IFN-y production from T cells, B cells, NK cells, macrophages and dendritic cells, especially in combination with IL-12.In contrast, without IL-12, IL-18 has capacity to induce IL4 and/or IL-13 secretion from NK cells, basophils and mast cells in vitro. We have shown that in the presence of IL-3, IL-18 causes basophils and mast cells to produce large amounts of IL-4, IL-13 and histamine. We have also revealed that naive CD4+ Tcells cultured with IL-2 and IL-18 for 4 days express CD40L and produce IL-4 and IL-13.for induction of IL-18-induced IL-4 and IL-13 production, we need no antigenic stimulation, such as FceR cross-linkage or TCR engagement. Moreover, IL-18-administered mice or IL-18 transgenic mice which endogenously accumulated IL-18 had high serum IgE and this production is dependent on CD4+ T cells, IL-4 and Stat6.These results taken together indicate that IL18 induce allergic disorders, particularly intrinsic atopic diseases characterized by the absence of particular antigen. We call this IL-18-induced allergic disorder as an innate type allergic response.We also found that injection of ovalbumin-specific TCR transgenic BALB/c mice (DOll.10) with a goat-anti-mouse anti-IgD Ab increases IgE production without Th2 polarization. This anti-IgD-induced IgE production on DOll.10 has been revealed to depend upon the intrinsic IL18 and requires IL-4.Finally, we evaluated the serum IL-18 levels from patients with atopic dermatitis and found that IL-18 levels in the sera from patients with atopic dermatitis were significantly elevated compared to those from healthy volunteers. These results indicate that IL18 may be critically involved in regulation of Th2-independent IgE production

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Tominaga, K., et al.: "IL-12 synergizes with IL-18 or IL-1β for IFN-γ production from human T cells"Int.Immunol. 12. 151-160 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohkusu, K., et al.: "Potentiality of Interleukin-18 as a useful reagent for the treatment and prevention of Leishmania major infection"Infect.Immunity. 68. 2448-2456 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamanaka, K., et al.: "Skin-specific caspase-1 transgenic mice show cutaneous apoptosis and pre-shock condition with a high serum level of IL-18"J.Immunol.. 165. 997-1003 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshimoto, T., et al.: "IL-18 induction of IgE : dependence on CD4^+T cells, IL-4 and STAT6"Nature Immunol.. 1. 132-137 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Naka, T. et al.: "socs (Suppressor Of Cytokine Signaling)-/SSI induced STAT Inhibitor)-1-dependent hepatic NKT cells participate in severe hepatitis through dysregulated cross-talk Inhibition of IFN-γ and IL-4 signaling In vi"Immunity. 14. 535-545 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Toshio, T.et al.: "Interleukin-18 is elevated in the sera from patients with atopic dermatitis and from atopic dermatitis model mice, NC/Nga"Int.Arch.Allergy and Immunol.. 125. 236-240 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakanishi, K., et al.: "Annual Rev.Immunol.(Paul, W.E., et al.eds.)"Annual Reviews. 52 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakanishi, K., Yoshimoto, T., Tsutsui, H.and Okamura, H.: "Interleukin-18 regulates both Th1 and Th2 responses."Annu. Rev. immunol.,. 19. 423-474 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakanishi, K., Yoshimoto, T., Tsutsui, H.and Okamura, H.: "Intreleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu."Cytokine & Growth Factor Rebiews.. 12. 53-72 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okamura, H., Tsutsui, H., Kashiwamura, S-I., Yoshimoto, T., and Nakanihi, K.: "Interleukin18."In : The Cytokine Reference, (Oppenheim, J. J., et al. eds.), Academic Press, London. 337-350 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okamura, H., Tsutsui, H., Kashiwamura, S-I., Yoshimoto, T., and Nakanihi, K.: "IL-18 receptor."In : The Cytokine Reference, (Oppenheim, J. J., et al. eds.), Academic Press, London. 1605-1609 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakanishi, K., Yoshimoto, T.,: "Potentiality of Interleukin-18 as a useful reagent for the treatment of infectious diseases."In : The Cytokine Therapeutics in Infectious Diseases, (Holland, S>M>eds.), Lippincott Williams & Wilkins, Philadelphia,. 119-144 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshimoto, T., Tsutsui, H., Okamura, H., Nakanishi, K.: "Measurement of human and mouse Interleukin-18"In : Current Protocols in Immunology (Coligan, J. E., Kruisbeek, A. M., Margulies, D. H., Shevach, E.. M. eds.), John Wiley & Sons, Inc., New York.. 6.26.1-12. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Naka, T. et al.: "SOCS (Suppressor Of Cytokine Signaling)-/SSI induced STAT Inhibitor)-1-dependent hepatic NKT cells participate in severe hepatitis through dysregulated cross-talk inhibition of IFN-γ and IL-4 signaling in vi"Immunity. 14. 535-545 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Toshio, T. et al.: "Interleukin-18 is elevated in the sera from patients with atopic dermatitis and from atopic dermatitis model mice, NC/Nga"Int. Arch. Allergy and Immunol.. 125. 236-240 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakanishi, K. et al.: "Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu"Cytokine & Growth Factor Reviews. 12. 53-72 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 善本知広, 中西憲司: "IL-18をめぐって-1L-18とアレルギー"Annu. Rev. 呼吸器 2001. 15-21 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 善本知広, 中西憲司: "IgE産生におけるIL-18の2面性"臨床免疫. 35. 452-458 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 善本知広, 中西憲司: "アレルギー性炎症におけるIL-18の役割"Molecular Medicine. 38. 512-518 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshimoto, T. et al.: "Measurement of human and mouse Interleukin-18. In : Current Protocols in Immunology"John Wiley & Sons. Inc.. 13 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hayashi,N., et al.: "Kupffer cells from Schistosoma mansoni-infected mice participate in the prompt type 2-differentiation of hepatic T cells in response to worm antigens."J.Immunol.. 163. 6702-6711 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tominaga,K., et al.: "IL-12 synergizes with IL-18 or IL-1β for IFN-γ production from human T cells."Int.Immunol.. 12. 151-160 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kodama,T., et al.: "IL-18 deficiency selectively enhances allergen-induced eosinophilia in mice."J.Allergy Clin.Immunol.. 105. 45-53 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohkusu,K., et al.: "Potentiality of Interleukin-18 as a useful reagent for the treatment and prevention of Leishmania majoy infection."Infect.Immunity. 68. 2448-2456 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamanaka,K., et al.: "Skin-specific caspasc-1 transgenic mice show cutaneous apoptosis and pre-shock condition with a high serum level of IL-18."J.Immunol.. 165. 997-1003 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshimoto,T., et al.: "IL-18 induction of IgE : dependence on CD4^+T cells, IL-4 and STAT6."Nature Immunol.. 1. 132-137 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okamura,H., et al.: "The Cytokine Reference (Oppenheim, J.J., et al.eds.)"Academic Press. 14 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakanishi,K., et al.: "Annual Rev.Immunol.(Paul, W.E., et al.eds.)"Annual Reviews. 52 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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