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Novel transcription factor to regulate differentiation of tracheal epithelial cells.

Research Project

Project/Area Number 09672239
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKumamoto University

Principal Investigator

KAI Hirofumi  Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (30194658)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsLYSOZYME / MEF / ETS / EPITHELIUM / 気道上皮細胞 / 分化 / 転写因子 / 肺胞上皮細胞 / アポトーシス
Research Abstract

We previously cloned and characterized the bovine lysozyme 5A (lys 5A) promoter with the purpose of determining cis-and trans-acting elements controlling airway epithelial cell-specific expression. We found that such expression is controlled by protein binding to an ets consensus sequence located-at-46/-40 from the transcription start site. The identity of the ets-related protein responsible for gene transactivation was unknown. In the present study, we screened ets-related proteins : MEF, ESE-1, Elf-1, Ets-1, Ets-2, and PEA 3 by transient transfection into epithelial cells and fibroblasts. Results showed that among these factors, MEF most strongly stimulated transcription in lung epithelial cells (A549), colon carcinoma cells (Caco2), and skin fibrobalsts (NIH3T3). Gel shift analysis of epithelial cell nuclear extracts using a lys 5A probe including the ets binding site (-50/-31) yielded a single band with retarded mobility. This band was supershifted by an antibody directed against MEF.This indicated that MEF is present in lung epithelial cells A549 and binds to the ets binding site in the lys 5A promoter. Supporting this, we found that anti-sense MEF mRNA decreased lys 5A promoter activity. Moreover, MEF overexpression in stable transfectants increased lysozyme mRNA and protein expression. In summary, these studies provide the first information identifying a transcription factor controlling lysozyme expression in epithelial cells. As bacteria become progressively more resistant to exogenously applied antibiotics, information regarding mechanisms controlling innate immunity, such as that provided by epithelial lysozyme, may offer important new therapeutic approaches.

Report

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

    (24 results)

All Other

All Publications (24 results)

  • [Publications] M.Okumura et al.: "Effects of eosinophil-granule major basic protein on phosphatidylcholine secretion in rat type II pneumocytes" Am.J.Physiol.(印刷中). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Kai et al.: "MEF up-regulates lysozyme transcription in epithelial cells" J.Biol.Chem.(印刷中). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Miyata,H.Kai et al.: "Current opinion of muco-active drug research : strategies and problems" Eur.Respir.J.11. 480-491 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Fukushima et al.: "Inhibition of glycine-induced current by morphine in nucleus tractus solitarii neurones of guinea-pigs" Meth.Find Exp.Clin.Pharmacol.20. 125-132 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Kido et al.: "The use of monoclonal antibodies to quantify airway mucin content in human bronchio-alveolar lavage fluid" Pharm.Pharmacol.Commun.4. 219-223 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Takahashi et al.: "Effects of SS320A,a new cysteine derivative,on the change in the number of goblet cells induced by isoproterenol" Jpn.J.Pharmacol.77. 71-77 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Okumuraa, H.Kai, S.Shinozawaa, Y.Isohama, and T.Miyata: "Effects of eosinophil-granule major basic protein on phosphatidylcholine secretion in rat type II pneumocytes" Am.J,Phisiol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Kai, A.Hisatsune, T.Chihara, A.Uto, A.Kokusho, T.Miyata, and C.Basbaum: "MEF up-regulates lysozyme transcription in epithelial cells" J.Biol.Chem.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Miyata, H.Kai, Y.Isohama, K.Takahama: "Current status of mucus drug research : Strategies and problems" Eur.Respir.J.11. 480-491 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Fukushima, S.Nagayama, M.Otsuka, K.Takahama, Y.Isohama, H.Kai and T.Miyata: "Inhibition of glycine-induced current by morphine in nucleus tractus solitarii neurones of the guinea-pig" Meth.Find.Exp.Clin.Pharmacol.20. 125-132 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Kido, H.Kai, N.Hara, I.Hamamura, Y.Isohama, K.Takahama and T.Miyata: "The use of monoclonal antibodies to quantify airway mucin content in human bronchio-alveolar lavage fluid" Pharm.Pharmacol.Comm.4. 219-223 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Takahashi, H.Mizuno, H.Ohno, H.Kai, Y.Isohama, K.Takahama, S.Nagaoka and T.Miyata: "Effects of SS320A,a new cysteine derivative, on the change in the number of goblet cells induced by isoproterenol in rat tracheal epithelium" Jpn.J.Pharmacol.77. 71-78 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Okumura et al.: "Effects of eosinophil-granule major basic protein on phosphatidylcholine secretion in rat type II pneumocytes" Am.J.Physiol. 印刷中. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Kai et al.: "MEF up-regulates lysozyme transcription in epithelial cells" J.Biol.Chem.印刷中. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Miyata,H.Kai et al.: "Current opinion of muco-active drug research:strategies and problems" Eur.Respir.J.11. 480-491 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Fukushima et al.: "Inhibition of glycine-induced current by morphine in nucleus tractus solitarii neurones of guinea-pigs" Meth.Find Exp.Clin.Pharmacol.20. 125-132 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Kido et al.: "The use of monoclonal antibodies to quantify airway mucin content in human bronchio-alveolar lavage fluid" Pharm.Pharmacol.Commun. 4. 219-223 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Takahashi et al.: "Effects of SS320A,a new cysteine derivative,on the change in the number of goblet cells induced by isoproterenol" Jpn.J.Pharmacol.77. 71-77 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T. Kido: "The use of monoclonal antibodies to quantify airway mucin content in human bronchioalveolar lavage fluid" Pharmac. Sci.印刷中. (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] K. Takahama: "Inhibition of glycine currents by dextromethorphan in neurons dissociated from the guinea-pig nucleus tractus solitarii" Br. J. Pharmacol.120. 690-694 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y. Isohama: "Dexamethasone increases β2-adrenoceptor-regulated phosphatidylcholine secretion in rat alveolar type II cells" Jpn. J. Pharmacol.73. 163-169 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K. Takahama: "Differential effect of codeine on coughs caused by mechanical stimulation of two different sites in the airway of guinea-pigs" Eur. J. Pharmacol.329. 93-97 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K. Kusano: "The effect of fudosteine, a new mucoactive drug, on the mucus secretion increased by several secretagogues in human pulmonary mucoepidermoid carcinoma cells" Pharm. Sci.3. 403-406 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] S. Tai: "Effect of human neutrophil elastase on tracheal mucociliary transport in anesthetized quails" Jpn. J. Pharmacol.75. 323-328 (1997)

    • Related Report
      1997 Annual Research Report

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

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