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Study on cell-to-cell interactions between airway epithelial cells and inflammatory cells in the pathogenesis of asthma

Research Project

Project/Area Number 07407072
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionUniversity of Tokyo

Principal Investigator

ITO Koji  UNIVERSITY of Tokyo, Dpt. of Med. dPhys. Therap. Professor, 医学部・附属病院, 教授 (10008310)

Co-Investigator(Kenkyū-buntansha) SHOJI Shunsuke  UNIVERSITY of Tokyo, Dpt. of Med. dPhys. Therap. Assistant Professor, 医学部・附属病院, 助手 (10171018)
TAKIZAWA Hajime  UNIVERSITY of Tokyo, Dpt. of Med. dPhys. Therap. Assistant Professor, 医学部・附属病院, 助手 (80171578)
SUKO Matsunobu  UNIVERSITY of Tokyo, Dpt. of Med. dPhys. Therap. Lecturer, 医学部・附属病院, 講師 (80107622)
OKUDAIRA Hirokazu  UNIVERSITY of Tokyo, Dpt. of Med. dPhys. Therap. Lecturer, 医学部・附属病院, 講師 (30106645)
MORITA Yutaka  UNIVERSITY of Tokyo, Dpt. of Med. dPhys. Therap. Associate Professor, 医学部・附属病院, 助教授 (60107620)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1996: ¥3,300,000 (Direct Cost: ¥3,300,000)
KeywordsBrochial Asthma / Airway Epithelium / T Cells / Mast Cells / Eosinophils / Cytokine Network / Repair / Remodeling / 気管支上皮細胞 / サイトカイン / フィブロネクチン / 接着因子
Research Abstract

Bronchial asthma is characterized by profound bronchoconstriction and persistent airway inflammation associated with hyperresponsiveness. There is a dense accumulation of eosinophils, mast cells and lymphocytes, whcih are belived to play important roles in the pathogenesis of asthma. We investigated the cell-to-cell interactions, especially between airway epithelial cells and the inflammatory cells in vitro. Airway epithelial cell-derived fibronectin, IL-8 and RANTES showed a chemotactic activity for mast cells, Iymphocytes and eosinophils, respectively. Airway epithelial cells also express and release IL-6 and GM-CSF which activate lymphocytes and eosinophils, and epithelium-derived endothelin-lshowed a potent bronchoconstricting action on airway smooth muscles.We further showed that eosinophil adhesion to bronchial epithelial cells is one of the important signals for eosinophil activation and degranulation.Airway epithelial cell growth and differentiation are crucial steps for the repair processes of airway mucosa, and failure of correct repair may result in tissue remodeling. We demonstrated that both eosinophils and epithelial cells express TGFbeta, whcih may be a factor to suppress normal repair and to induce remodeling in the airways. We believe our findings gave new insights into the cell-to-cell interactions important in the thogenesis of asthma, and may help develop better strategies for the treatment of this disease.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] Ito,K.: "Treatment of acute bronchial asthma attack" Asian Med.J.39(5). 227-238 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kitani,S.,Teshima,R.,Nonomura,Y.,Morita,Y.,Ito,K.: "The effect of okadaic acid on histamine release,cell morphology,phosphorylation in rat basophilic leukemia (RBL-2H3) cells,human basophils and rat peritoneal mast cells." Int.Arch.Allergy Immunol.110. 339-347 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mori,A.,Suko,M.,Kaminuma,O.,Inoue,S.,Ohmura,T.,Nishizaki,Y.,Nagahori,T.,Asakura,Y.,Hoshino,A.,Okumura,Y.,Sato,G.,Ito,K.,Okudaira,H.: "IL-15 promotes cytokine production of human T helper cells." J.Immunol.156. 2400-2405 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takafuji,S.,Ohtoshi,T.,Takizawa,H.,Tadokoro,K.,Ito,K.: "Eosinophil degranulation in the presence of bronchial epithelial. Cells effect of cytokines and role of adhesion." J.Immunol.156. 3980-3985 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takizawa,H.,Ohtoshi,T.,Yamashita,N.,Oka,T.,Ito,K.: "Interluekin-6 receptor expression in human bronchial epithelial cells." Am.J.Physiol 270 (Lung Cell.Mol.Physiol.14). 270. L346-352 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sato,M.,Takizawa,H.,Kohyama,T.,Ohtoshi,T.,Takafuji,S.,Kawasaki,S.,Tohma,S.,Ishii,A.,Shoji,S.,Ito,K.: "Eosinophil adhesion to human bronchial epithelial cell : regulation by cytokines." Int.Arch.Allergy Immunol.1997. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 滝沢始: "気道上皮細胞に対する作用-サイトカイン生産、炎症・免疫とマクロライドUp to Date(清水喜八郎、他編)" 医薬ジャーナル社, 4 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 滝沢始: "気道上皮細胞の傷害と修復;成長因子・サイトカインの役割について(宮本昭正編)" Asthma-an inflammatory disease,Excerpta Medica, 10 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ito, K.: "Treatment of acute bronchial asthma." Asian Med. J.39. 227-238 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kitani, S., Teshima, R., Nonomura, Y., Morita, Y., Ito, k.: "The effect of okadaic acid on histamine release, cell morphology, phosphorylation in rat basophilic leukemia (RBL-2H3) cells, human basophils and rat peritoneal mast cells." Int. Archv. Allergy Immunol.110. 339-347 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mori, A., Suko, M., Kaminuma, O., Inoue, S., Ohmura, T., Nishizaki, Y., Nagahori, T., Asakura, Y., Hoshino, A., Okumura, Y., Sato, G., Ito, K., Okudaira, H.: "IL-15 promotes cytokine production of T helper cells." J.Immunol.156. 2400-2405 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tkafuji, S., Ohtoshi, T., Takizawa, H., Tadokoro, K., Ito, K.: "Eosinophil degranulation in the presence of bronchial epithelial cells. - effect of cytokines and role of adhesion." J.Immunol.156. 3980-3985 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Takizawa, T.Ohtoshi, N.Yamashita, T.Oka, K.Ito: "Interleukin-6 receptor expression in human bronchial epithelial cells." Am. J.Physiol.270. L346-352 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sato M,Takizawa H,Kohyama T,Ohtoshi T,Takafuji S,Kawasaki S,Tohma S,Ishii A,Shoji S,Ito K.: "Eosinophil adhesion to human bronchial epithelial cells : regulation by cytokines." Int. Arch. Allergy Immunol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hajime, Takizawa.: "The effect on bronchial epithelial cells. In K.Shimizu, et al editors. Cytokine production, inflammation, immunology and macrolide." Igaku Journal. (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hajime, Takizawa.: The damage and repair of bronchial epithelial cells.In T.Miyamoto, et al editors. The role of growth factor and cytokine : Asthma-an inflammatory disease, Excerpta Medica, (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ito,K.: "Treatment of acute bronchial asthma attack" Asian Med.J.39(5). 227-238 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kitani,S.,Teshima,R.,Nonomura,Y.,Morita,Y.,Ito,K.: "The effect of okadaic acid on histamine release,cell morphology,phosphorylation in rat basophilic leukemia(RBL-2H3)cells,human basophils and rat peritoneal mast cells" Int.Arch.Allergy Immunol.110. 339-347 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] mori,A.,Suko,M.,Kaminuma,O.,Inove,S.,Ohmura,T.,ishizaki,Y.,Nagahori,T.,Asakura,Y.,Hoshino,A.,Okumura,I.,Sato,G.,Ito,K.,Okudaira,H.: "IL-15 promotes cytokine production of human Thelper cells" J.Immunol.156. 2400-2405 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takafuji,S.,Ohtoshi,T.,Takizawa,H.,Tadokoro,K.,Ito,K.: "Eosinophil degranulation in thepresence of bronchial epithelial cells effect of cytokines and role of adhesion" J.Immunol.156. 3980-3985 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takizawa,H.,Ohtoshi,T.,Yamashita,N.,Oka,T.,Ito,K.: "Interleukin-6 receptor expression in human bronchial epithelial cells" Am.J.Physiol^<270>(Lung cell.Mol.Physiol.14). 270. L346-352 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sato,M.,Takizawa,H.,Kohyama,T.,Ohtoshi,T.,Takafuji,S.,Kawasaki,S.,Tohma,S.,Ishii,A.,Shoji,S.,Ito.K.: "Eosinophil adhesion to human bronchial epithelial cells:regulation by cytokines" Int.Arch.Allergy Immunol,1997. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 滝沢 始: "気道上皮細胞に対する作用-サイトカイン産生、炎症・免疫とマクロライドVp to Date(清水喜八郎他編)" 医薬ジャーナル社, 4 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 滝沢 始: "気道上皮細胞の傷害と修復;成長因子・サイトカインの役割について(宮本昭正編)" Asthma-an inflammatory disease.Excerpta Medica, 10 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takizawa,H.,Desaki,M.,Ito,K.,et al.: "Erythromycin suppresses interleukin 6 expression by human bronchial epitheliall cells." Biochem.Biophys.Res.Commun.210. 781-786 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takizawa,H.,Ohtoshi,T.,Ito,K.,et al.: "Histamine octivates bronchial epithelial cells to release in flammatory cytokines in vitro." Int.Archv.Appl.Immund.108. 260-268 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takizawa,H.,Ohtoshi,T.,et al.: "Interleukin-6 receptor expression in human bronchial epithelial cells." Am.J.Physiol.(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 滝沢始,大利隆行,伊藤幸治,他: "ヒト気道上皮細胞のサイトカイト発現および産生に対するマクロライド抗生物質の影響" 日気食会報. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 幸山正,滝沢始,伊藤幸治,他: "好酸球のIL-8産生に対するマクロライド系抗生物質の影響" The Japanese Journal of Antibiotics. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shoji,S.,et al.: "Cigarette smoke stimulates releess of neutrophil chemotactic octivity from cultured bovine bronchial epithelial cells." Clinied Science. 88. 337-344 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 岡崎仁,滝沢始,伊藤幸治,他.: "気道上皮からのIL-8産生の方向性に及ぼすDEP(Diesel Exhaust Partides)の影響" 臨床呼吸生理. 27. 37-44 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mori,A.,Suko,M.,Okudaira,H.,et al.: "Interleukin-5 production by CD4 T cells of asthmatic patients is suppressed by qlucocorticoids and the immunosuppressant FK506 and cyclosporin A." Int.Immunol.7. 449-453 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mori,A.,Suko,M.,Okudaira,H.,et al.: "Allergen specific T cell clones produce IL-5 upon stimulation with Th1 cytokive,IL-2." Int.Arch.Allergy Immunol.107. 220-222 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mori,A.,Okudaira,H.,Ito,K.,et al.: "Aralysis of human IL-5 gene transcription by T cell cloves and hydridomas." Int.Arch.Allergy Immunol.107. 366-367 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Okudaira,H.,Mori,H.,Ito,H.,et al.: "Evhanced production and gene expression of IL-5 in Patients with brovchial asthma-possible management of atopic diseases by downregulation of IL-5 gen tionscriptic." Int.Arch.Allergy Immunol.107. 255-258 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nagai,S.,Morita,Y.,et al.: "Pharmacological study of stem cell factor-induced mast cell histamine release with kinase tnhibitors." Biochem.Biophys.Res.Commun.208. 576-581 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Miyamasu,M.,Morita,Y.,et al.: "Chemotactic agonists induce cytokine production in eosinephils." J.Immunol.154. 1339-1349 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamaguchi.M.,Morita,Y.,et al.: "A beta2-agonist,procaterol inhibits bosophil migration." J.Asthma.32. 125-130 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 滝沢始: "喘息の基礎から臨床まで(伊藤幸治編)/気道上皮の役割" 医薬ジャーナル社(大阪), 75-79(309) (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 滝沢始: "Annual Review 呼吸器(工藤翔二、他編)/14員環マクロライド抗生物質の抗炎症作用" 中外医学社(東京), 184-191 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 滝沢始: "炎症、免疫とマクロライドUp to Date(清水喜八郎,他編)/気道上皮細胞に対する作用-サイトカイン産生" 医薬ジャーナル社(東京)(in press), (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mori,A.,Ito,K., Okudaira,H.,et al.: "Molecular Biology of Allergens and the Atopic Immune Rospovse (A.Sehon,et al.ed)/Enhanced production and gene expression of IL-5 in bronchial asthma-possible management of atopic disease with IL-5 specific gene transription inhibitor." Plenum Press(New York)(in press), (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Okudaira,H.,Mori,A.,Suko,M.,et al.: "Progress in Allergy and Clinical Immunclogy Vol.3(S.G.O.Johonsson ed/Treatment of atopic diseases with glucocorticoids,cyclosporin A and FK506." Hogrefe & Huber Publishers(Germeny), 311-316 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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