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Cl ion transport and CFTR gene expression in antigen sensitized airway epithelium

Research Project

Project/Area Number 10670564
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionTokyo Women's Medical University

Principal Investigator

KONDO Mitsuko  Tokyo Women's Medical University, Dept. of Medicine, Assistatnt Professor, 医学部, 講師 (50178430)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordssensitization / airway epithelium / Cl ion / ion transport / CFTR / histamine / remodeling / IL-4 / Clイオン / ヒスダミン
Research Abstract

1. Antigen challenge increases C1 ion transport in sensitized guinea pig trachea
Antigen challenge causes hypersecretion in asthma. Allthough various mediators involved in asthma stimulate C1 ion transport, the direct effect of antigen challenge on C1 ion transport remains unclear. The short circuit current (Isc) in the presence of amiloride was measured in Ussing chamber in sensitized guinea pig tracheas. Ovalbumin (OA)-challenge induced monophasic increase in Isc. Pretreatment of the trachea with pyrilamine, but not cimetidine significantly inhibited OA-challenge induced increase in Isc (△Isc) in a dosedependent manner. Pretreatment with FK224 or sodium cromogycate also inhibited OA-induced △Isc. These data suggest that activation of sensitized mast cells by antigen challenge releases histamine, which increases C1 ion transport through direct epithelial action and via sensory C-fibers.
2. Repeated antigen sensitization induces epithelial remodeling and elevation of C1 transport by CFTR upregulation in guinea pig trachea ; the role of IL-4
To elucidate the mechanism of hypersecretion in chronic remodeled asthmatic airway, guinea pigs were injected with OA weekly four weeks, and assessed on the 6th week. Goblet cell hyperplasia, Isc in the presence of amiloride in Ussing chamber and CTFR-positive epithelial cells were significantly increased in sensitized trachea as compared with the control animals. These changes were inhibited by dexamethasone, Th2 inhibitor, or anti IL-4 antibody. We concluded that 1) repeated antigen sensitization and challenges induce goblet cell hyperplasia and elevation of Cl ion transport by upregulated CFTR expression, 2) Th2 cytokines, especially IL-4 may be involved in these mechanisms, 3) steroid and Th2 inhibitor may be useful for the treatment of hypersecretion in chronic asthma.

Report

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

    (17 results)

All Other

All Publications (17 results)

  • [Publications] M. kondo et al: "Antigen challenge increases CL ion transport in sensitized guinea pig trachea."Proceeding of airway secretion research. 1. 77-81 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M. kondo et al: "Remodeled tracheal epithelium after repeated sensitization is ready for hypersecretion in guinea pigs."Am. J. Respir. Crit. Care Med.. 159. A37 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M. kondo et al: "Erythromycin inhibits ATP-induced intracellular calcium responses in bovine tracheal epithelial cells."Am. J. Respire. Cell Moll. Biol.. 19. 799-804 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S.kanoh, M. Kondo et al: "Effect of FK506 on ATP-induced intracellular calcium oscillations in cow tracheal epithelium."Am. J, physiol.. 276. L891-L899 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M.Kondo, J.Tamaoki, S. Kanoh, et al.: "Antigen challenge increases Cl ion transport in sensitized guinea pig trachea."Proceeding of airway secretion research. 1. 77-81 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M.Kondo, J.Tamaoki, J.Nakata, A. Nagai: "Remodeled tracheal epithelium after repeated sensitization is ready for hypersecretion in guinea pigs."Am. J. Repir. Crit. Care Med.. 159. A37 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M.Kondo, S.Kanoh, J. Tamaoki, H. Shirakawa, S.Miyazaki, A.Nagai: "Erythromycin inhitis ATP-induced intracellular calcium responses in bovine tracheal epithelial cells."Am. J. Respir. Cell Mol. Biol.. 19. 799-804 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S.Kanoh, M.Kondo, J.Tamaoki, et al.: "Effect of FK506 on ATP-induced intracelluar calcium oscillations in cow tracheal epithelium."Am. J. Physiol.. 276. L891-L899 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M.Kondo et al: "Antigen challenge increases Cl ion transport in sensitized guinea pig trachea"Proceeding of airway secretion research. 1. 77-81 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Kondo et al: "Remodeled tracheal epithelium after repeated sensitization is ready for hypersecretion in guinea pigs"Am. J. Respir. Crit. Care Med.. 159. A37 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 近藤光子: "気道上皮のリモデリングと気道分泌亢進"アレルギー. 48. 229 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 近藤光子: "反復抗原感作による気道上皮のリモデリングと気道分泌亢進"日本呼吸器学会雑誌. 37. 191 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 近藤光子: "反復抗原投与後の気道上皮リモデリングに対する抗IL-4抗体の抑制効果"日本呼吸器学会雑誌. 38. 113 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 近藤光子: "イオンチャンネル.呼吸器疾患の分子生物学"医学書院,川上義和,谷口直之,木田厚瑞編. 187〜199 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mitsuko Kondo et al: "Erythromycin inhibits ATP-induced Intracellular calcium responses in bovine tracheal epithelial・cells" Am.J.Respir.cell Mol.Biol.19. 799-804 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mitsuko Kondo et al: "Remodeled tracheal epithelium after repeated sensitization is ready for hypersecretion in guined pigs" Am.J.Respir.Crit.Care Med.159. in press (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 近藤光子 他: "反復抗原感作による気道上皮のリモデリングと気道分泌亢進" 日本呼吸器学会雑誌. 37. 191 (1999)

    • Related Report
      1998 Annual Research Report

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

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