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炎症性サイトカインとそのレセプター遺伝子発現機序の解析とその制御

Research Project

Project/Area Number 07672375
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKyoritsu University of Pharmacy

Principal Investigator

笠原 忠  共立薬科大学, 薬学部, 教授 (60049096)

Co-Investigator(Kenkyū-buntansha) 向田 直史  金沢大学, がん研, 助教授 (30182067)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywords炎症性サイトカイン / インターロイキン-8 / ケモカイン / 血管内皮細胞 / ミエローマ / 核内転写因子 / 単球走化因子 / IL-8 / MCAF(MCP-1) / 好酸球
Research Abstract

私共はIL-1やTNFによって誘導されるIL-8、MCAFなどの炎症性サイトカインがin vitroおよびin vivoでの役割を明らかにするため、本研究を行い、以下のような成果を得た。
(1)種々の培養細胞におけるIL-8/MCP-1/JEおよびその遺伝子発現の解析を行った。とくに、ヒト好酸球で、IL-8産生を見たところ、Ca5の処理によって著名なIL-8産生が見られた(Miyamasuら 、'95)。また、ヒトHL-60をレチノール酸およびDMSOによって好中球に分化させるとIL-8産生能が増大し、IL-8R発現の増加が見られた。さらに、IL-8遺伝子発現へのシグナル伝達を調べる目的で、NF-kBとのゲルシフト法を検討した(園田、論文投稿中)。
(2)動脈硬化発症解析の一環として、ヒト血管内皮細胞と好中球・単球との接着におけるケモカインの関与を検討した。すなわち、血管内皮細胞は単球との接着によりIL-8およびMCP-1/JEを産生することをELISA、ノーザンブロットおよび免疫組織化学染色により明らかにした(Takahashiら、'95,'96,'97;Seinoら'95)。さらに脳腫瘍における炎症性サイトカイン発現について培養グリオーマ細胞株において検討を行った(Kasaharaら、投稿中)。
(3)ヒトMCP-1/JE cDNAをBCMGSneoをミエローマ細胞株で発現させた。この細胞株をヌードマウスに移植し、in vivoにおける抗腫瘍増殖効果を検討したところ、腫瘍の周辺に単球・マクロファージが浸潤すると共に、単球の増加が観察された(Hoshinoら,'95)。また、IL-8RタイプA,Bを発現させ、これに対する特異抗体を作製した後、骨髄分化段階におけるIL-8レセプターの発現の解析を行った(Wangら,'96)。本研究について今後の継続課題としたい。

Report

(2 results)
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Hoshino,Y.,Katake,K.,Kasahara,T.et al.: "Monocyte chemoattractant protein-1stimulates tumor necrosis and recruitment of macrophages into tumor in tumor-bearing nude mice : Increased granulocyte……" Experimental Hematology. 23. 1035-1039 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ko.,Y・C.,Mukaida,N.,Kasahara,T.et al.: "Specific elevation IL-8 levels in peritoneal dialysate of patients on continuous ambulatory peritoneal dialysis(CAPD) with peritonits." J.Clin.Pathol.48. 115-119 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Miyamasu,M.,Hirai,K.,Kasahara,T.et al.: "Chemotactic agonists inducecytokine generation in eosinophils." J.Immunol.154. 1339-1349 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Seino,Y.,Ikeda,U.,Kasahara,T.et al.: "Expression of monocyte chemoattractant protein-1 in vascular tissue." Cytokine. 7. 575-579 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sugiyama.Y.,Kasahara,T.,Mukaida,N.et al.: "Chemokine in bronchoalveolar lavage fluid from the patients with summer-type hypersensitivity pneumonitis." Eur.Respir.J.8. 1084-1090 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takahashi,M.,Masuyama,J-I.,Kasahara,T.,et al.: "Induction of monocyte chemoattractant protein-1 synthesis in human monocytes during transendothelial migration in vitro." Circulation Res.76. 750-757 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yasumoto,K.,Mukaida,N.,Kasahara,T.,et al.: "Molecular analysis of the cytokine network involved in cachexia in colon 26 adenocaricinoma-bearing mice." Cancer Res.55. 921-927 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Azuma,E.,Yuo.A.,Kasahara,T.,et al.: "Activation and priming og human monocytes by monocyte chemotactic and activating factor : Cooperation with other inflammatory cytokkines and close association increase……" Expt.Hematol.24. 169-175 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takahashi,M.,Ikeda,U.,Kasahara,T.,et al.: "Monocyte-endothelial cell interaction induces expression of adhesion molecules on human umbilical cord endothelial cells." Cardiovas.Res.32. 422-429 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Wang,J-B.,Zhang,Y.,Kasahara,T.,et al.: "Detection of mouse IL-8 receptor homologue expression on peripheralblood leukocytes and mature myeloid lineage cells in bone marrow." J.Leukoc.Biol.60. 372-381 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takahashi,M.,Ikeda,U.,Kasahara,T.,et al.: "Activation of human monocytes for enhanced production of IL-8 during transendothelial migration in in vitro." J.Clin.Immumol.17. 53-61 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Miyamasu,M.,Misaki,Y.,Hirai,K.,Kasahara,T.et al.: "Eosinophilopoietic factors prime eocinophilis for increased IL-8 generation." Allergy. (5). in press (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 笠原 忠、小田泰子: "サイトカイン実験法 サイトカインの定量法と機能解析" 羊土社, 82-86 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 笠原 忠、園田よし子: "サイトカイン実験法 サイトカインの定量法と機能解析" 羊土社, 164-169 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Seino, Y.,: "Expression of cytokine-Induced neutrophil chemoatractant in rat cardiac myocytes" J. Mol. Cell. Cardiol.27. 2043-2051 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fujioka, N.: "Preparation of specific antibody agains murine IL-1RA and the establishment of IL-1RA as an endogenous regulator of bacteeria-induced fulminant hepatitis in mice" J. Leuk. Biol.58. 90-98 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takahashi, M.: "Effects of endogenous endothelial IL-8 on neutrophol migration across an endothelial monolayer" Cardiovas. Res.29. 670-675 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Seino, Y.: "Expression of monocyte dhmoatractant protein-1 in vascular tissue" Cytokine. 7. 576-579 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hoshino, Y.: "MCP-1 stimulates tomor necrosis and recruitmemt of macrophages into tumors in tumor bearing nude mice" Exp. Hematol.23. 1035-1041 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Miyamasu, M.: "Chemotactic agonists induce cytokine generation in eosinophils" J. Immunol.154. 1339-1349 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 笠原 忠、高橋将文: "ケモタクシスの機序" 医学のあゆみ 医歯薬出版, p.610-615 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 荒川洋一、笠原 忠: "サイトカインとアポトーシス" 臨床医 中外医学社, p.37-40 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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