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ヒト気道防御物質の局在と分泌機構の解明

Research Project

Project/Area Number 10470149
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

志村 早苗  東北大学, 医学部・附属病院, 講師 (20154312)

Co-Investigator(Kenkyū-buntansha) 山谷 睦雄  東北大学, 医学部・附属病院, 助手 (60261640)
佐々木 司  東北大学, 医学部・附属病院, 講師 (10241598)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2000: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
Keywordsヒト / 気管支腺 / 気道上皮細胞 / クロライドイオンチャンネル / ムチン / リゾチーム / グルコステロイド / マクロライド / サーファクタントプロティンA / デフェンシン / 遺伝子発現 / ムチン遺伝子 / クロライドチャンネル / Secretory leukoprotease Inhibitor
Research Abstract

手術肺および死後4時間以内の剖検肺から得られた気道を用いて、気道上皮細胞および気管支腺(粘膜下腺細胞)を単離し、また各々の培養細胞を作製した。これらの細胞とHuman pulmonary mucoepidermoid carcinoma cell line(NCI-292)を用いて、次のような所見を得た。すなわち、1)リゾチーム、Secretory leukocyte protease inhibitor(SLPI)のいずれもCFTR発現、クロライドチャネルとしての機能に明瞭な影響を及ぼさなかった。2)リゾチーム、SLPI、サーファクタントプロティンA(SP-A)、デフェンシン(hBD)の遺伝子発現あるいは分泌に於いて、呼吸器疾患を有しない例、慢性気管支炎例および気管支喘息例間で明瞭な差異は認められなかった。3)ステロイドであるデキサメサゾン処理でSLPIの分泌および遺伝子発現、ムチンのMUC1,MUC2,MUC4,MUC5ACの遺伝子発現のいずれも有意に抑制した。14員環系マクロライドであるエリスロマイシン処理ではSLPIの分泌および遺伝子発現が抑制されず、むしろ増強させられる傾向を示した。また、エリスロマイシンは免疫機構に働くとされているMUC1の遺伝子発現を増強させたが、分泌顆粒のムチンであるMUC4,MUC5ACの遺伝子発現のいずれも有意に抑制した。以上の所見は主に気管支腺、NCI-292で明瞭にみられたが、気道上皮細胞ではそれらの分泌量および遺伝子発現が少なく明瞭でなかった。

Report

(3 results)
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] 玉田勉: "A novel function of thyrotropin as a potentiator of electrolyte secretion from tracheal gland"American Journal of Respiratory Cell and Molecular Biology. 22. 566-573 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 斉藤弘樹: "Gene expression and secretion of secretory leukocyte protease inhibitor by human shbmucosal gland cell."American Journal of Physiology : Lung Cellular and Molecular Biology. 280. L79-L87 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 志村早苗: "Signal transduction of mucous secretion by bronchial gland cells"Cellular Signalling. 12. 271-277 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 志村早苗: "Extracellular ATP regulation of airway secretion"Drug Development Research. 52(in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 笠森寛: "Cyclic ADP-ribose, a novel Ca^<2+>-mobilizing second messenger operates in airway gland acinar cells in vitro"Journal of Biological Chemistry. in press. (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 斉藤弘樹: "Proceeding of Airway Secretion Research"Dunes Co.Press, Tokyo. 98 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 色川 俊也: "Cholinomimetic action of macrolide antibiotics on airway gland electrolyte secretion"American Journal of Physiology: Lung Cellular and Molecular Physiology. 276. L951-L957 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 玉田 勉: "A novel function of thyrotropin as a potentiator of electrolyte secretion from tradual gland"American Journal of Respiratory Cell and Melecular Biology. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 斉藤弘樹: "Gene expression and secretion of secretory lenkocyte protease inhibitor by submucosal gland"American Journal of Physiology: Lung Cellular and Moleculer Biology. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 笠森 寛: "Cyclic ADP-ribose, a novel Ca^<2+>-mobilizing second messenger, operates in airway gland acinar cells in vivo"Journal of Clinical Inrestigation. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 志村 早苗: "Signal transduction of mucous secretion by bronclial gland cells"Cellular Signalling. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 志村 早苗: "Goblet 細胞"呼吸. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 志村 早苗: "Proceeding of Airway Secretion Research"Dunes Co. Press,Tokyo. 172 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 斉藤弘樹: "Proceeding of Airway Secretion Research"Dunes Co. Press,Tokyo. 印刷中 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 斉藤 弘樹: "Surfactant protein A2 gene expression by human submucosal gland cells" American Journal of Respiratory Cell and Molecular Biology. 19. 202-209 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 山本 稔: "Laminin inhibits iscproterenol-induced Cl^-secretion across canine tracheal epithelium" Respiration Physiology. 114. 277-284 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 色川 俊也: "Choliomimetic action of macrolide antibiotics on airway gland electrolyte secretion" American Journal of Physiology:Lung Cellular and Molecular Physiology. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 志村 早苗: "気道の防御機構:気管支腺の役割" 日本気管食道科学会会報. 49. 97-102 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 志村 早苗: "Signal transduction in airway epithelial and gland cells" Cellular Signalling. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 志村 早苗: "粘液分泌細胞" 医学のあゆみ,呼吸器疾患:State of Arts. Ver.3. 5522-5525 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 志村 早苗: "Proceeding of Airway Secretion Research(in press)" 高坂知節編集,帝人医薬出版,東京, (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 笹森 寛: "気道壁の病態" 泉 孝英編集,メディカルジャーナル社,東京, 70 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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