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Basic research for the onset and modulation of allergic diseases

Research Project

Project/Area Number 10470486
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionGifu pharmaceutical University

Principal Investigator

NAGAI Hiroichi  Gifu pharmaceutical University, Professor, 薬学部, 教授 (90082974)

Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsbronchial asthma / atopic dermatitis / gene engineering mice / Th2 cytokines / lipid mediator / leukotriene / histamine / retinoid / アレルギー / 気道過敏症 / 好酸球 / プロスタグランジン / IgE / IL-5 / IL-4 / サイトカイン / 抗アレルギー薬 / ステロイド薬
Research Abstract

The purpose of present study is to know the onset mechanism of allergic reaction diseases. In the first step, we produced a suitable model for bronchial asthma and atopic dermatitis in the animals. We produced a suitable model for bronchial asthma and atopic dermatitis in the animals. We have established a bronchial asthma model in guinea pigs and mice. Both animals were immunized with antigen, and then they were exporsed to aerolized antigen 3 to 5 times. They showed an asthmatic sympton in the respiratory tract and allergic disorders in the lung tissues. In addition, we produced two kinds of atopic dermatitis models in mice. Mice showed high serum, IgE, eczemtic symptons in the skin and itching behavior. These symptoms are similar to clinical symptoms. In the second step, we investigated a function molecule for the onset of allergic disorders by employing above models in gene engineering mice. We found the importance of lipid mediator, especially leukotrienes and cytokines including IL-4 and IL-5. In the third step, we revealed the efficacy of luteolin, one of flavonoids, on experimental allergic reactions. Luteolin showed strong anti-allergic effect mainly due to the inhibition of MAP-kinase activation and calcium movement. We are now still investigating a functional molecule for the onset of allergic diseases by using a certain kind of enzyme, and receptor gene knockout mice.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Nagai h et al.: "Role of mast cells in the onet of IgE-mediated late phase cutaneous response in mice."J.Allergy Clin Immun.. 106. S91-S98 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuoka T et al.: "Prostaglandin D_2 as a mediator of allergic asthma."Science. 287. 2013-2017 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] kobayashi T et al.: "An essential role of mast cells in the development of airway hyperresponsiveness in a murine asthma model."J.Immunol.. 164. 3855-3861 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagai H et al.: "Different role of IL-4 in the onset of hapten-induced contact hypersensitivity in BALB/c and C57BL/6 mice."Brt.J.Pharmacol.. 129. 299-306 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawakami et al.: "Terreic acid, a quinone epoxide inhibitor of Bruton's tyrosine kinase."Proc.Natl.Acad. Sci.USA.. 96. 2227-2232 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hata D et al.: "Involvment of Bruton's tyrosine kinase in Fcε RI-dependent mast cell degranulation and cytokine production."J.Exp.Med.. 187. 1235-1247 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagai H, Ueda Y, Ochi T, Hirano Y, Tanaka H, Inagaki N, Kawada K: "Different role of IL-4 in the onset of hapten-induced contact hypersensitivity in BALB/c and C57BL/6 mice."J.Allergy Clin.Immun.. 106. S91-98 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuoka T, Hirata M, Tanaka H, Takahashi Y, Murata T, Kabashima K, Sugimoto Y, Kobayashi T, Ushikubi F, Aze Y, Eguchi N, Urade Y, Yoshida N, Kimura K, Mizoguchi A, Honda Y, Nagai H, Narumiya S: "Prostaglandin D_2 as a mediator of allergic asthma."Science. 287. 2013-2017 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kobayashi T, Miura T, Haba T, Sato M, Serizawa I, Nagai H, Ishizaka K: "An essential role of mast cells in the development of airway hyperresponsiveness in a murine asthma model."J.Immunol.. 164. 3855-3861 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagai H, Abe T, Yamaguchi I, Mito K, Kimata M, Inagaki N: "Role of mast cells in the onset of IgE-mediated late phase cutaneous response in mice."Brt.J.Pharmacol.. 129. 299-306 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawakami Y, Hartman S.E.Kinoshita E, Suzuki H, Kitaura J, Yao L, Inagaki N, Franco A, Hata D, Yamamoto-Maeda M, Fukamachi H, Nagai H, Kawakami T: "Terreic acid, a quinone epoxide inhibitor of Bruton's tyrosine kinase."Proc.Natal.Acad.Sci.USA.. 96. 2227-2232 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hata D, Kawakami Y, Inagaki N, S.Lantz C, Kitamura T, N.Khan W, Maeda-Yamamoto M, Miura T, Han W, E.Hartman S, Tao L, Nagai H, E.Goldfeld A., W.Alt F, J.Galli S, N.Witte O, Kawakami T: "Involvement of Bruton's tyrosine kinase in FcεRI-dependent mast cell degranulation and cytokine production."J.Exp.Med.. 187. 1235-1247 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagai H et al.: "Role of mast cells in the onet of IgE-mediated late phase cutaneous response in mice."The Journal of Allergy and Clinical Immunology. 106. S91-S98 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsuoka T et al.: "Prostaglandin D_2 as a mediator of allergic asthma."Science. 287. 2013-2017 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kobayashi T et al.: "An essential role of mast cells in the development of airway hyperresponsiveness in a murine asthma model."Journal of Immunology. 164. 3855-3861 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kimata et al.: "Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells."Clinical and Experimental Allergy. 30. 501-508 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nagai H et al.: "Different role of IL-4 in the onset of hapten-induced contact hypersensitivity in BALB/c and C57BL/6 mice."British Journal of Pharmacology. 129. 299-306 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kimata et al.: "Effect of luteoline and other flavonoids on IgE-mediated allergic reactions."Planta Medica. 66. 25-29 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Inagaki,N.,Nagai,H.et al.: "Participation of histamine H_1 and H_2 receptors in passive cutaneous anaphylaxis-induced scratching behavior in ICR mice."Eur.J.Pharmacol.. 397. 361-371 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawakami,Y.,Nagai,H.et al.: "Terreic acid,a quinone epoxide inhibitor of Bruton's tyrosine kinase"Proc.Natl.Acad.Sci.. 96. 2227-2232 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kimata,M.,Nagai,H.et al.: "Ca^<2+> and protein kinase C signaling for histamine and sulfidoleukotrienes released from human cultured mast cells"Biochem.Biophyls Res. Commun.. 80. 859-900 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shichijo,M.,Nagai,H.et al.: "Role of cvclic3'.5'-adenosine monophosphate in the regulation of chemical mediator release and cytokine production from cultured human mast cells"J.Allergy Clin.Immunol.. 103. 421-428 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takizawa,T.,Nagai,H.et al.: "Effect of a new antiallergic agent,VUF-K-8788,on experimental asthmatic reactions in guinea pigs"Pharmacology. 59. 127-134 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagai,H.,Ueda,Y.et al.: "Different role of IL-4 in the onset of hapten-induced contact hyersensitivity in BALB/c and C57BL/6 mice"Brt.J.Pharmacol.. 129. 299-306 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tanaka,H.et al.: "Effect of anti-IL-4 and IL-5 antibodies on allergic airway hyperresponsiveness in mice" Life Science. 62. 169-174 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nagai,H et al.: "Effect of Byakko-ka-ninjin-to on experimental allergic cutaneous reactions" J.Trad.Med.15. 208-215 (1998)

    • Related Report
      1998 Annual Research Report

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

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