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担癌宿主に於けるサイトカインネットワーク分子機構の解析

Research Project

Project/Area Number 05151028
Research Category

Grant-in-Aid for Cancer Research

Allocation TypeSingle-year Grants
Research InstitutionKanazawa University

Principal Investigator

松島 綱治  金沢大学, がん研究所, 教授 (50222427)

Co-Investigator(Kenkyū-buntansha) 横田 崇  東京大学, 医科学研究所, 助教授 (50134622)
栗林 景容  三重大学, 医学部, 教授 (10064578)
藤原 大美  大阪大学, 医学部・附属バイオメディカル教育研究センター, 助教授 (70116094)
審良 静男  大阪大学, 細胞生体工学センター, 助手 (50192919)
向田 直史  金沢大学, がん研究所, 助教授 (30182067)
Project Period (FY) 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥16,000,000 (Direct Cost: ¥16,000,000)
Fiscal Year 1993: ¥16,000,000 (Direct Cost: ¥16,000,000)
Keywordsサイトカイン / 癌病態 / 産生制御 / 生体工学
Research Abstract

担癌宿主に於ける種々の癌病態を制御するサイトカインネットワーク分子機構の解析として以下のような成果があった。1)マウス大腸癌細胞株colon26のin vitroとin vivoにおけるサイトカイン産生を比較したところ大きく異なることが判明した。更に、悪疫質をおこす株では選択的にIL6をin vivoで発現し、おこさない株ではIL6の産生がみられずIL1 receptor antagonistの発現が観られた。2)担癌宿主では腫瘍由来TGFbによるCD4+Thのサイトカイン産生抑制に加えIL6がMoによるTNF産生を抑制して抗腫瘍生体防御能を低下させていることがわかった。3)CD4+のCTL誘導抑制性Tsの存在を明らかにし、CTL標的抗原を決定した。4)ヒト胸腔内Moが癌性胸水中リンパ球のIL2による活性化を増強するとともにIL12がCD8+Tリンパ球よりCTLを誘導する時もMoが関与することを明らかにした。5)gp130,NF-IL6ノックアウトマウスを作製した。6)癌病態調節サイトカインIL8,IL6の遺伝子発現調節機構を詳細に解明した。in vitroとin vivo(癌部位)におけるサイトカイン産生検索は、サイトカインネットワーク解析の仕事はin vivoを想定してのみなしうることを示した。今後更に担癌にともないどのようなサイトカインが実際に発現されるのか、その産生細胞はどれか、実際にin vitroの観察から予想されているようなサイトカインネットワークが存在するのかを種々の癌細胞株を用いたマウスでのモデル実験を行なうとともにヒト癌においても検証する必要がある。サイトカイン遺伝子発現調節機構解析、受容体シグナル伝達機構解析の基礎研究をサイトカイン遺伝子、受容体遺伝子、転写因子、シグナル伝達分子ノックアウトマウス作製の仕事と連結し、サイトカインネットワーク機構解析のためのよいモデル動物を提供できることを期待する。

Report

(1 results)
  • 1993 Annual Research Report

Research Products

(63 results)

All Other

All Publications (63 results)

  • [Publications] Hirose,K.,et.al.: "Overexpression of mitochondrial manganese superoxide dismutase promotes the survival of tumor cells exposed to interleukin 1,tumor necrosis factor,selected anticancer drugs,and ionizing radjation." FASEB J.7. 361-368 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ko,Y.-C.,et al.: "Elevated IL-8 level in the urine of patients with urinary tract infections." Infect.Immunol.61. 1307-1314 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Morita,M.,et.al.: "Induction and regulation of IL-8 and MCAF production in human brain tumor cell lines and brain tumor tissues." Eur.Cytokine Netw.4. 351-358 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Maruyama,H.,et.al.: "Murine endothelial cell line cells,F-2:Interaction with leukocytes and cytokines production." Microbiol.Immunol.37. 895-903 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yoshioka,K.,et.al.: "In situ expression of cytokines in IgA nephritis." Kidney International. 44. 825-833 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Jinquan,T.,et.al.: "Human IL-10 is a chemoattractant for CD8+ T lymphocytes and an inhibitor of IL-8 induced CD4+T lymphocyte migration." J.Immunol.151. 4545-4551 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Abe,Y.,et.al.: "Transient rise in serum interleukin-8 concentration during acute myocardial infarction." British Heart J.70. 132-134 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tsuchiya,I.,et.al.: "Induction of inflammatory cytokines in the pleural effusin of cancer patients after the administration of an immunomodulator OK-432:role of IL 8 and C5a for neutrophil infiltration." Cytokine. (in press.).

    • Related Report
      1993 Annual Research Report
  • [Publications] Harada,A.,et.al.: "Expression of recombinant rabbit IL-8 in Escherichia coil and establishment of the essential involvement of IL-8 in recruiting neurtophils into lipopolysaccaride-induced inflammatory site of rabbit skin." Int.Immunol.5. 681-690 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kuno,K.,et.al.: "Structure and function of the intracellular portion of the mouse interleukin 1 receptor(type 1)." J.Biol.Chem.268. 13510-13518 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Taub,D.D.,et.al.: "Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T Lymphocytes and promotes T cell adhesion to endothelial cells." J.Exp.Med.177. 1809-1814 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Gusella,G.L.,et.al.: "IL-2 up-regulates but IFN-γ suppresses IL-8 expression in human monocytes." J.Immunol.151. 2725-2732 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sekido,N.,et.al.: "Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against interleukin-8." Nature. 365. 654-657 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Akahoshi,T.,et.al.: "Expression of monocyte chemotactic and activating factor in rheumatoid arthritis." Arthritis and Rheumatism.36. 762-771 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nomura,H.,et.al.: "Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte chemotactic peptide receptors." Int.Immunol.5. 1239-1249 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Matsusaka,T.,et.al.: "NF-IL6 and NF-kB synergistically activate transcription of the inflammatory cytokines,IL-6 and IL-8." Proc.Natl.Acad.Sci.U.S.A.90. 10193-10197 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sigh,R.K.,et.al.: "Synergism between human monocyte chemotactic and activating factor and bacterial products for activation of tumorcidal properties in murine macrophages." J.Immunol.151. 2786-2793 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Horiguchi,H.,et.al.: "Cadmium induces interleukin-8 production in human peripheral blood mononuclear cells with the concomitant generation of superoxide radicals." Lymphokine and cytokine research. 12. 421-428 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Morita,M.,et.al.: "Induction and regulation of IL-8 and MCAF production in human brain tumor cell lines and brain tumor tissues." Eur.Cytokine Netw.4. 351-358 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Okamoto,S.,et.al.: "The interleukin-8 AP-1 and kB-like sites are genetic end targets of FK506-sensitive pathway accompanied by calcium mobilization." J.Biol.Chem.(in press.). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mukaida,N.,et.al.: "A novel mechanism of glucocorticoid-mediated gene repression:nuclear factor-kB site is the target for glucocorticoid-mediated interleukin 8 gene repression." J.Biol.Chem.(in press.).

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakano,Y.,et.al.: "Protection of lethal bacterial infection in mice by monocyte chemotactic and activating factor(MCAF)." Infect.Immun.(in press.).

    • Related Report
      1993 Annual Research Report
  • [Publications] Nielsen,B.W.,et.al.: "Macrophage as producer of chemotactic proinflammatory cytokines." Macrophage pathogen interactions.131-142 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Okamoto,S.,et.al.: "Molecular mechanism of interleukin 8 gene expression." IIIrd International Symposium of Chemotactic Cytokines.(in press.).

    • Related Report
      1993 Annual Research Report
  • [Publications] Kyo,S.,et.al.: "NF-IL6 represses early gene expression of human papillomavirus type 16 through the binding to the non coding region." J.Virology. 67. 1058-1066 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakajima,T.,et.al.: "Phosphorylation at threonine 235 by a ras-dependent MAP kinase cascade is essential for transcriptional activation of NF-IL6." Proc.Natl.Acad.Sci.USA. 90. 2207-2211 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nishio,Y.,et.al.: "A nuclear factor for interleukin-6 expression(NF-IL6)and the glucocorticoid receptor synergistically activate transcription of the rat α1-acid glycoprotein gene via direct protein-protein interaction." Mol.Cell.Biol.13. 1854-1862 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Akira,S.,et.al.: "Interleukin-6 in biology and medicine." Advances in Immunology. 54. 1-78 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Betts,J.C.,et.al.: "The role of NF-kB and NF-IL6 transactivating factors in the synergistic activation of human serum amyloid A gene expression by interleukin-1 and interleukin-6." J.Biol.Chem.268. 25624-25631 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kishimoto,T.,et.al.: "Interactions of cytokines with the receptor family." Cell. 76. 253-262 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sugihara,S.,et.al.: "Thyroiditis-inducing T cell lines and clones derived from autoimmune thyroiditis lesions induced in mice by the elimination of regulatory T cell subset." J.Immunol.150. 683-694 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Li,X-F.,et.al.: "Transforming growth factor-β(TGF-β)-mediated immunosuporession in the tumor-bearing state:Enhanced production of TGF-β and a progressive increase in TGF-β susceptibility of anti-tumor CD4+T cell function." Jpn.J.Cancer Res.84. 315-325 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Iwata,H.,et.al.: "Suppression of allograft responses by combining donor alloantigen-specific i.v.presensitization with suboptimal doses of FK506." Transplantation. 56. 173-180 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Fujiwara,H.,et.al.: "Role of thymic stromal cells in inducing T cell differentiation in the thymus." Proc.of 3rd International Symposium on Immunotherapy. in press. (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nagata,T.,et.al.: "Suppression of anti-tumor CD4+T cell responsiveness in the tumor-bearing state and its recovery by maintaining in the in vitro cultures free of tumor burden." Jpn.J.Cancer Res.84. 1181-1189 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kita,Y.,et.al.: "Thymic stroma-derived T cell inhibitory factor(TSTIF).I.TSTIF induces inhibition of antigen-stimulated T cell proliferation." Thymus-J.of T cell Biology. 21. 159-175 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tai,X-G.,et.al.: "Thymic stroma-derived T cell inhibitory factor(TSTIF).II.TSTIF acts on the antigen-stimulated cell to inhibit antigen-stimulated T cell proliferation." Thymus-J.of T cell Biology. 21. 247-258 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Zou,J-P.,et.al.: "Recovery of anti-tumor CD4+T cell responsiveness suppressed in the tumor-bearing state by release from tumor burden." J.Cancer Res.Clin.Oncol.(in press). (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Uehira,M.,et.al.: "The development of dermatitis infiltrated by as T cells in IL-7 transgenic mice." Int.Immunol.5. 1619-1627 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Iwata,H.,et.al.: "Suppression of allograft responses by combining alloantigen-specific i.p.presensitization with suboptimal doses of FK506 or rapamycin." Transplant.Proc.(in press). (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Narumiya,S.,et.al.: "Pre-B cells adhere to fibronectin via interactions of VLA-5/vitronectin receptor with RGDS as well as of VLA-4 with V region sequences at its different binding sites." Int.Immunol.6. 139-147 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Iwata,H.,et.al.: "Suppression of allograft responses by combining alloantigen-specific i.v.presensitization with suboptimal doses of rapamycin." Int.Immunol.6. 93-99 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mizuhara,H.,et.al.: "T cell activation associated hepatic injury:Mediation by tumor necrosis factor and protection by interleukin-6." J.Exp.Med.(in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Teramura,Y.,et.al.: "Interferon-γ-producing tumor induces host tumor-specific T cell responses." Jap.J.Cancer Res.84. 689-696 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Iwashiro,M.,et.al.: "Multiplicity of virus-encoded helper T-cell epitopes expressed on FBL-3 tumor cells." J.Virol.67. 4533-4542 (1933)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yanagawa,S.,et.al.: "Mouse mammary tumor virus with rearranged long terminal repeats causes murine lymphomas." J.Virol.67. 112-118 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Uenaka,A.,et.al.: "Roles of CD8+ and CD4+ cells on lethal graft-versus-host disease in nude mice." Transplant Immunol.1. 132-136 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Morioka,A.,et.al.: "Effects of non-major histocompatibility complex background genes on the induction of CD4+T cells that prevent rejection of a highly immunogenic tumor,FBL-3." Int.Immunol.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakagawa,Y.,et.al.: "Inhibition of MAIDS development by the transplantation of bone marrow cells carrying Fv-4 resistant gene to the MAIDS virus-infected mice." J.Virol.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Suzuki,M.,et.al.: "Reconstitution of anti-tumor effects of Lentinan in nude mice:Roles of DTH reaction triggered by CD4 positive T cell clone in the infiltration of effector cells into tumor." Jap.J.Cancer Res.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Koyano-Nakagawa,N.,et.al.: "Reconstitution of the functional GM-CSF promoter:Evidence for distinct activation mechanisms that mediate the response to phorbol ester/calcium and HTLV-Tax signals." Int.Immunol.5. 345-352 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Lee H-J.,et.al.: "cAmp activates the IL-5 promoter synergistically with phorbol ester through the signaling pathway involving protein kinase A in mouse thymoma line EL-4." J.Immunol.151. 6135-6142 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Watanabe,S.,et.al.: "Reconstituted human granulocyte-macrophage colony-stimulating factor(GM-CSF)receptor transduces growth promoting signals in mouse NIH3T3 cells:Comparison with signalling in BA/F3 proB cells." Mol.Cell.Biol.13. 1440-1448 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Watanabe,S.,et.al.: "Differential Regulation of c-fos,c-jun and c-myc Protooncogenes through Human Granulocyte Macrophage Colony-Stimulating Factor Recepter in BA/F3 pro-B cells and NIH3T3 cells:Selective Activation of c-fos Promoter by Genistein." Mol.Biol.Cell.4. 983-992 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yokota,T.,et.al.: "Reconstitution of functional human GM-CSF receptor in mouse NIH3T3 fibroblast and BA/F3 proB cells." Leukemia. 7. S102-S107 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hironaka,T.,et.al.: "Structural study of the Sugar chains of porcine factor VIII;tissue-and species-specific glycosylation of factor VIII." Arch.Biochem.Biophys.307. 316-330 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takahashi,K.,et.al.: "Conversion of G-protein specificity of insulin-like growth factor II/mannose 6-phosphate receptor by exchanging of a short region with beta-adrenergic receptor." Proc.Natl.Acad.Sci.USA. 90. 11772-11776 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masuda,E.,et.al.: "GM-CSF,IL-3,IL-4 and I1-5:Regulation of genes and signal transduction by their receptors." Molecular Biology of Hematopoiesis. Vol3(in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Arai,K.,et.al.: "Hematopoietic growth factors on human chromosome 5:genes and their receptors." J.Cell.Biochem.(in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Lee,H.J.,et.al.: "Signals and nuclear factors that regulate the expression of interleukin 4 and interleukin 5 genes in helper T cells." J.Allergy and Clinical Immunology Supplement. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Chen,J.X.,et.al.: "Activation of early response genes and cell proliferation by human IL-3,GM-CSF,and IL-5 receptors:comparison with human IL-4 receptor signaling." J.Allergy and Clinical Immunology Supplement. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Koyano-Nakagawa,N.,et.al.: "Molecular cloning of a novel human cDNA encoding a zinc finger protein that binds to the interleukin 3 promoter." Mol.Cell.Biol.(in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakagawa,Y.,et.al.: "Structure of the gene encoding the a subunit of the human granulocyte macrophage colony stimulating factor receptor:implications for the evolution of the cytokine receptor superfamily." J.Biol.Chem.(in press).

    • Related Report
      1993 Annual Research Report

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Published: 1993-03-31   Modified: 2016-04-21  

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