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Study of the mechanisms for chronic allergic disease and application to drug research

Research Project

Project/Area Number 09672267
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionTOKUSHIMA BUNRI UNIVERSITY

Principal Investigator

AKAGI Masaaki  Dep.of Pharmacol., Fac.of Pharm.Sci., TOKUSHIMA BUNRI UNIVERSITY Professor, 薬学部, 教授 (90093658)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsAllergic Inflammation / Mast cells / Histamine / Chemokines / Eosinophils / 活性酸素 / 鼻アレルギー / サイトカイン
Research Abstract

Female Hartley guinea pigs were used. Guinea pigs were sensitized using egg albumin, and 14 days after, antigen solution was applied to the nasal mucosa. Immediate type of allergic reaction, the increase of vascular permeability, the sneezing and the scratching, was elicited. The nasal septum was collected, sectioned and stained using Luna staining 6, 12, 24, 48, 72hrs after application. l2hrs after, the accumulation of eosinophils significantly increased in nasal mucosa. The increase was significantly inhibited by anti-PAF and anti-LT drugs, and partially inhibited by anti-histamines, And the increase of expression of MIP-1 alpha mRNA was induced in nasal mucosa. Because we have observed the increase of expression of MIP-1 alpha mRNA in rat peritoneal mast cells induced by antigen-antibody reaction, the results suggest the contribution of mast cells to the expression of MIP-1 alpha mRNA in nasal mucosa. When histamine was applied to the nasal mucosa of non-sensitized guinea pigs, eosinophils were accumulated through H1 receptors, as well as that induced by antigen-antibody reaction. Hydrogen peroxide also increased the expression of MIP-1 alpha mRNA in mast cells and the increase was inhibited by catalase. And I confirmed the binding sites of superoxide-associated transcription factors in the promotor region of MIP-1 alpha. These results suggest that in the chronic allergic disease, histamine and superoxide released from mast cells induced by antigen-antibody reaction through IgE may enhance the production of chemokine such as MIP-1 alpha in the peripheral cells and the accumulated eosinophils may contribute to the prolongation and enlargement of the allergic disease.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] N.Fukuishi et al: "The mechanisms of compound 48/80 -induud saperoeide-" Biochem.Mol.Med.61. 107-113 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Akagi et al: "Inhibitory effect of apafant on brouchopulmounry.." Arznein.-Forsch./Drug Ros.47. 1364-1369 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 赤木正明: "ヒスタミンの気管支喘息" 日薬理誌. 111. 217-222 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 赤木正明 他: "アレルギー性疾患における肥満細胞の活性酸素--" 日薬理誌. 112. 73-77 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] N.Fukuishi, M.Sakaguchi, S.Matsuura, C,Nakagawa, R.Akagi and M.Akagi: "The mechanisms of compound 48/80-induced superoxide generation mediated by A-kinase in rat peritoneal mast cells." Biochem.Mol.Med.61. 101-113 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Akagi, E.Nishioka, R.Kanoh, M.Tachibana and N.Fukuishi: "Inhibitory effect of apafant on bronchopulmonary responses to platelet activating factor and to antigen in rats." Arzneim.-Forsch./Drug Res.47. 1364-1369 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Akagi: "Histamine in the pathogenesis of asthma." Folia Pharmacol. Jpn.111. 217-222 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Akagi, N.Fukuishi, M.Sakaguchi, N.Matsui, H.Takahashi: "Role of superoxide generation and degradation system of mast cells in allergic inflammation." Folia Pharmacol. Jpn.112. 73P-77P (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] N.Fukuishi et al.: "The mechanisms of compound 48/80-induced superoxirle" Biochem.Mol.Med.61. 107-113 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Akagi et al.: "Inhibitory effect of apafant on bronchopulusunry" Arzneim.-Forsch./Drug Res.47. 1364-1369 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 赤木正明: "ヒスタミンと気管支喘息" 日薬理誌. 111. 217-222 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 赤木正明他: "アレルギー性炎症における肥満細胞の活性酸素" 日薬理誌. 112. 73P-77P (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Akagi, N.Fukuishi et al: "Anti-allargic effect of Tea-leaf saponin from tea leases." Biol, Pharm, Bull,. 20(5). 565-567 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] N.Fukuishi et al: "The mechanisins of compound 48/80-induced superpkide・・・・・" Biochem. Mol,Med.61. 107-113 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Akagi et al: "Inhibitory effect of apafant on bronchspulmonary susponses・・・・・" Arzneum. Forsch. /Drug Res,. 47. 1364-1369 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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