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1996 Fiscal Year Final Research Report Summary

Cellular Detachment and Deformation induce Cytokine Gene Expression in Human Bronchial Epithelial Cells

Research Project

Project/Area Number 07670654
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionYamagata University

Principal Investigator

NAKAMURA Hidenori  Yamagata University School of Medicine, Assistant Professor, 医学部, 講師 (30240675)

Co-Investigator(Kenkyū-buntansha) SATA Makoto  Yamagata University School of Medicine, Instructor, 医学部, 助手 (00280892)
KATO Shuichi  Yamagata University School of Medicine, Instructor, 医学部, 助手 (90260463)
Project Period (FY) 1995 – 1996
KeywordsInterleukin-8 / Bronchial epithelial cells / Cellular detachment / Microtuble / Neutrophil elastase
Research Abstract

Neutrophil elastase (NE) is known to be one of the most potent proteases capable of deforming and detaching human bronchial epithelial cells (BECs) and inducing interleukin-8 (IL-8) gene expression. However, mechanisms of NE-induced IL-8 gene expression are unclear, especially with respect to how they relate to cellular detachment. In order to elucidate these mechanisms, effects of cell detachment and deformation following mechanical injury or pharmacological stimuli on IL-8 gene expression were examined by Northern analyzes. When BET-1A cells from a human bronchial epithelial cell line were incubated with NE (100nM), trypsin (0.5mg/ml), EGTA (7mM) or EDTA (0.7mM) to induce deformation and detachment, IL-8 mRNA transcript levels were upregulated as demonstrated in a case of mechanical detachment from the culture plate using a cell scraper. These IL-8 gene expression was inhibited by pretreatment with 5mM taxol, a microtubule stabilizing agent. Colchicine or vinblastine, microtubule disrupting agents, induced IL-8 gene expression, which was also inhibited by taxol treatment. These data suggest that structural changes, including deformation of the cytoskeleton, especially microtubules, may contribute to IL-8 gene expression in human BECs. Since detachment and cellular deformation of BECs caused by proteases have been frequently observed in a variety of inflammatory airway diseases, our findings provide evidence that detached or deformed BECs potentially enhance production of inflammatory mediators in the pathogenesis of airway inflammation.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Shibata Y,Nakamura H et.al: "Cellular Detachment and Deformation induce IL-8 Gene Expression in Human Bronchial Epithelial Cells" The Journal of Immunology. 156. 772-777 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura H et al: "Tumour Necrosis Faetor receptor gene expression and Shedding in human whole lung tissue and Pulmonary epithelium" European Respiratory Journal. 9. 1643-1647 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura H et al.: "Inhibition of neutrophil-elastase induced interleukin-8 gene experession by urinary trypsin inhibitor in human bronchial epithelial cells" International Archives of Allergy and Immunology. 112. 157-162 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 阿部修一・中村秀範: "メディエーターとその周辺 -IL-8-" 診断と治療. 84. 2452-2454 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura H et al.: "Elevated levels of cytokeratin 19 in the bronchoalveolar lavage ttuid of patients with chronic airway inflammatory diseases" American Journal of Respiratory and Critical Care Medicine. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hino T,Nakamura H et.al: "Elevated level of type II soluble TNF receptor in bronchodvedar lavage fluid with sarcoidosis patients" Lung. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shibata Y,Nakamura H,Kato S,Tomoike H: "Cellular detachment and deformation induces interleukin-8 gene expression in human bronchial epithelial cells." Journal of Immunology. 156. 772-777 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inage M,Takahashi H,Nakamura H,Masakane I,Tomoike H: "Hypersensitivity pneumonitis induced by spores of Pholiota Nameko." Internal Medicine. 35. 301-304 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura H,Hino T,Shibata Y,Kato S,Takahashi H,Tomoike H: "Tumor necrosis factor receptor gene expression and shedding in whole lung tissue and pulmonary epithelium." Europian Respiratory Journal. 9. 1643-1647 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura H,Abe S,Shibata Y,Sata M,Kato S,Saito H,Hino T,Takahashi H,Tomoike H: "Inhibition of neutrophil-elastase induced interleukin-8 gene expression by urinary trypsin inhibitor in human bronchial epithelial cells." International Archieves of Allergy and Immunology. 112. 157-162 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura H,Abe s, Shibata Y,Yuki H,Suzuki H,Saito H,Sata M,Kato S,Tomoike H: "Elevated levels of cytokeratin 19 in the bronchoalveolar lavage fluid of patients with chronic airway inflammatory disease. A specific marker for bronchial epithelial injuries." Am J Respir Critical Care Med. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hino T,Nakamura H,Shibata Y,Abe S,Kato S,Tomoike H: "Elevated level of type II,soluble tumor necrosis factor receptor in bronchoalveolar lavage fluid with sarcoidosis patients." Lung. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nozaki N,Yamaguchi S,Shirakabe M,Nakamura H,Tomoike H: "Soluble tumor necrosis factor receptors are elevated in relation to severity of congestive heart failure." Jap Circ J. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Abe S,Nakamura H: "Interleukin-8." SINDAN TO CHIRYO. 84. 2452-2454 (1996)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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