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Molecular Mechanism of Barrier Function Changes of Epithelial Tight Junction in Allergic Rhinitis

Research Project

Project/Area Number 12671660
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionMie University

Principal Investigator

TAKEUCHI Kazuhiko  Mie Univ., Faculty of Medicine, Lecturer, 医学部・附属病院, 講師 (50206942)

Co-Investigator(Kenkyū-buntansha) KISHIOKA Chikako  Mie Univ., Faculty of Medicine, Assistant, 医学部, 助手 (10314113)
MAJIMA Yuichi  Mie Univ., Faculty of Medicine, Professor, 医学部, 教授 (60024791)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordsepithelium / permeability / tight junction / thrombin / leukotrienes / transepithelial resistance / histamine / allergic rhinitis / 密着結合蛋白 / 鼻粘膜 / horeseradish peroxidase
Research Abstract

1. We examined the effect of histamine, leukotriene D4 (LTD4) and thrombin on the epithelial permeability to 14C labeled mannitol and albumin using Calu-3 cell lines. 10^<-6>M LTD4 did not change permeability to mannitol or albumin. On the other hand, histamine and 10^<-7>〜10^<-8> M thrombin significantly increased epithelial permeability to mannitol. Moreover, 10^<-4>M histamine significantly increased the passage of horseradish peroxidase across epithelial tight junction in guinea pig nose.
2. Next we examined if histamine and thrombin can alter mRNA expression of tight junction proteins. We added histamine or vehicle to cultured human nasal epithelial cells and extracted RNA from them 4 hours later. After DNase treatment, mRNAs of β-actin and ZO-1 tight-junction protein were amplified by RT-PCR. Histamine significantly downregulated ZO-1 mRNA expression. This effect was blocked by pretreatment with mepyramine, an H1 receptor antagonist. Next we examined the effect of thrombin on the tight junction proteins mRNAs expression in cultured epithelial cells. Thrombin significantly decreased ZO-1 mRNA expression of the cells, but had no effect on the expression of occludin or claudin mRNAs. The reduction of ZO-1 mRNA by histamine and thrombin may cause increased permeability of the mucosa during allergic reactions in the nose.

Report

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

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Kazuhiko Takeuchi, et al.: "Histamine Alters Gene Expression in Cultured Human Nasal Epithelial Cells"J Allergy Clin Immunol. 107. 310-314 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kazuhiko Takeuchi, et al.: "Histamine Alters Gene Expression in Cultured Human Nasal Epithelial Cells"J Allergy Clin Immunol. 107(2). 310-314 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kazuhiko Takeuchi, et al.: "Histamine Alters Gene Expression in Cultured Human Nasal Epithelial Cells"J Allergy Clin Immunol. 107(2). 310-314 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kazuhiko Takeuchi, et al: "Histamine Alters Gene Expression in Cultured Human Nasal Epithelial Cells"J Allergy Clin Immunol. (in press).

    • Related Report
      2000 Annual Research Report

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

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