1994 年度実績報告書

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

研究課題

研究課題/領域番号	06282108
研究機関	金沢大学
研究代表者	松島綱治金沢大学, がん研究所, 教授 (50222427)
研究分担者	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)
キーワード	サイトカイン / 癌 / 免疫不全 / 生体工学 / 遺伝子発現
研究概要	サイトカインはホルモン様活性ポリペプチドであり、サイトカインの産生異常により様々な炎症疾患、免疫、血液異常が起こることが判明している。正常細胞の癌化、癌細胞の増殖、転位、担癌に伴う悪液質や免疫不全症にもサイトカイン産生産生異常が深く関与するものと推定されている。本研究班は担癌宿主におけるサイトカインネットワーク機構の総合的分子細胞生物学的解析を班研究で行っている。本年度の主な成果として 1)マウス大腸癌による悪液質誘導においてIL6の関与は部分的であり他の因子も関与することが明らかになった。また、悪液質誘導性クローンに特異的に発現する新しい遺伝子を4つPCR-differential display mathodによってクローニングした。 2)様々なサイトカインの発現を制御するNFkBのcell free系での活性化システムを確立した。 3)IL 12が強力な抗腫瘍活性を示すことが判明した。 4)CD4+TsのCTL前駆細胞の抑制にサイトカインが関与する事を示すとともに、CTL認識H-2Db結合性ペプチドのアミノ酸配列を決定した。 5)TH1,TH2特異的サイトカイン遺伝子の発現制御機構をIL2.IL5遺伝子で明らかにした。 6)NF-IL6欠損マウスマクロファージにおいてNOの産生が正常であるにもかかわらずリステリアの食菌能、抗腫瘍活性が低下していることが判明した。

研究成果

(28件)

すべてその他

すべて文献書誌 (28件)

[文献書誌] Okamoto,S-I.,et.al.: "The interleukin-S AP-1 and kB-like sites are genetic end targets of FK506-sensitive pathway accompanies by calcium mobilization." J.Biol.Chem.269. 8582-8589 (1994)
[文献書誌] Mukaida,N.,et.al.: "Novel mechanism of Glucocorticoid-mediated gene repression:nuclear factor-kB is target for glucocorticoid-mediated interleukin 8 gene repression." J.Biol.Chem.269. 13289-13295 (1994)
[文献書誌] Nakano,Y.,et.al.: "Protection against lethal bacterial infection in mice by monocyte-chemotactic and activating factor(MCAF)." Infect.Immunol.62. 377-383 (1994)
[文献書誌] Wada,T.,et.al.: "Prevention of proteinuria by the administration of anti-interleukin 8 antibody in experimental acute immune complex-induced glomerulonephritis." J.Exp.MeD.180. 1135-1140 (1994)
[文献書誌] Murayama,T.,et.al.: "Enhancement of human cytomegalovirus replication in a human lung fibroblast cell line by interleukin 8." J.Virol.68. 7582-7585 (1994)
[文献書誌] Yasumoto,K.,et.al.: "Molecular analysis of cytokine network involved in cachexia colon 26 adenocarcinoma-bearing mice." Cancer Res.55. 921-927 (1995)
[文献書誌] Yamamoto,K.,et.al.: "Regulatory mechanisms for production of interferon-γ and tumor necrosis factor by anti-tumor T cell or macrophages in the tumor-bearing state." J.Immunol.(in press).
[文献書誌] Shimizau,T.,et.al.: "Fine structure of a virus-encoded helper T cell epitope expressed on FBL-3 tumor cells." J.Viol.68. 7704-7708 (1994)
[文献書誌] Morioka,A.,et.al.: "Effects of non-MHC background genes on the induction of CD4+T cells that prevent rejection of a highly immunogenic tumor,FBL-3." Int.Immunol.6. 839-846 (1994)
[文献書誌] Kobayashi.Y.,et.al.: "Expression and function of multidrug resistance P-glycoprotein in a cultured natural killer cell-rich population revealed by MRK16 monoclonal antibody and AHC-52." Biocem.Pharmacol.48. 1641-1646 (1994)
[文献書誌] watanabe,N.,et.al.: "Selective release of a processed from interleukin 1α." Cytokine. 6. 597-601 (1994)
[文献書誌] Fujiwara,H.,et.al.: "The absence of IgE antibody-mediated augmentation of immune responses in CD23-deficient mice." Proc.Natl.Acad.Sci.UAS. 91. 6835-6839 (1994)
[文献書誌] Ishikawa,Y.,et.al.: "Establishment of lipopolysaccharide-dependent nuclear factor-kB activation in a cell-free system." J.Biol.Chem.270. 4158-4164 (1995)
[文献書誌] Kishimoto,T.,et.al.: "Cytokine signal transduction." Cell. 76. 253-262 (1994)
[文献書誌] Akira,S.,et.al.: "Molecular cloning of APRF,a novel IFN-Stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway" Cell. 71. 63-71 (1994)
[文献書誌] Tanaka,T.,et.al.: "Targeted disruption of the NF-IL6 gene discloses its essential role in bacteria killing and tumor cytotoxicity by macrophages." Cell. (in press). (1995)
[文献書誌] 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.120. 279-285 (1994)
[文献書誌] Mizuhara,H.,et.al.: "T cell activation associated hepatic injury:Mediation by tumor necrosis factor and protection by interleukin-6." J.Exp.Med.179. 1529-1537 (1994)
[文献書誌] Kawabe,T.,et.al.: "Immunoglobulin class switching and germinal center formation are impaired in CD40-deficient mice." Immunity. 1. 167-178 (1994)
[文献書誌] Tsuruta,R.,et.al.: "cAMP inhibits expression of the IL-2 gene through the NF-AT sequence and transfection of NF-AT cDNAs abrogates the sensitivity of EL-4 cells to cAMP." J.Immunol.(in press).
[文献書誌] Kinoshita,T.,et.al.: "Suppression of apoptotic death in hematopoietic cells by signaling through the IL-3/GM-CSF receptors." EMBO J.14. 266-275 (1995)
[文献書誌] Nabioullin,R.,et.al.: "Induction mechanism of human blood CD8+T cell proliferation and cytotoxicity by natural killer cell stimulatory factor(interleukin-12)." Jpn.J.Cancer.Res.86. 853-861 (1994)
[文献書誌] Haku,T.,et.al.: "Human alveolar macrophages augment natural killer cell stimulatory factor(interleukin-12)-inducible killer actibity from autologous blood lymphocytes." Jpn.J.Cancer.Res.86. 81-87 (1995)
[文献書誌] Yano,S.,et.al.: "Differential effects of anti-inflammatory cytokines(IL-4,IL-10 and IL-13)on tumoricidal.and chemotactic properties of human monocytes induced by monocyte chemotactic and activating factor." J.Leukoc.Biol.(in press).
[文献書誌] Takeuchi,A.,et.al.: "Purification and Characterization of a Human Erythrocyte-derived Growth Factor with a Wide Target Cell Spectrum." J.Biol.Chem.269. 24935-24940 (1994)
[文献書誌] Takeuchi,A.,et.al.: "A human erthrocyte-derived growth promoting factor with a wide target cell spectrum:Identification as catalase." Cancer Res.(in press). (1995)
[文献書誌] Watanabe,S.,et.al.: "Regulation by dietary essential fatty acid balance of tumor necrosis factor production in mouse macrophages." J.Leukoc.Biol.53. 151-156 (1993)
[文献書誌] Watanabe,S.,et.al.: "Regulation by lipopolysaccharaide-induced tumor necrosis α factor production by endogenous prostaglandin E2 in rat resident and thioglycollate-elicited macrophage." J.Lipid.Mediat.10. 283-294 (1994)

1994 年度 実績報告書

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

研究代表者

松島 綱治 金沢大学, がん研究所, 教授 (50222427)

研究成果

[文献書誌] Okamoto,S-I.,et.al.: "The interleukin-S AP-1 and kB-like sites are genetic end targets of FK506-sensitive pathway accompanies by calcium mobilization." J.Biol.Chem.269. 8582-8589 (1994)

[文献書誌] Mukaida,N.,et.al.: "Novel mechanism of Glucocorticoid-mediated gene repression:nuclear factor-kB is target for glucocorticoid-mediated interleukin 8 gene repression." J.Biol.Chem.269. 13289-13295 (1994)

[文献書誌] Nakano,Y.,et.al.: "Protection against lethal bacterial infection in mice by monocyte-chemotactic and activating factor(MCAF)." Infect.Immunol.62. 377-383 (1994)

[文献書誌] Wada,T.,et.al.: "Prevention of proteinuria by the administration of anti-interleukin 8 antibody in experimental acute immune complex-induced glomerulonephritis." J.Exp.MeD.180. 1135-1140 (1994)

[文献書誌] Murayama,T.,et.al.: "Enhancement of human cytomegalovirus replication in a human lung fibroblast cell line by interleukin 8." J.Virol.68. 7582-7585 (1994)

[文献書誌] Yasumoto,K.,et.al.: "Molecular analysis of cytokine network involved in cachexia colon 26 adenocarcinoma-bearing mice." Cancer Res.55. 921-927 (1995)

[文献書誌] Yamamoto,K.,et.al.: "Regulatory mechanisms for production of interferon-γ and tumor necrosis factor by anti-tumor T cell or macrophages in the tumor-bearing state." J.Immunol.(in press).

[文献書誌] Shimizau,T.,et.al.: "Fine structure of a virus-encoded helper T cell epitope expressed on FBL-3 tumor cells." J.Viol.68. 7704-7708 (1994)

[文献書誌] Morioka,A.,et.al.: "Effects of non-MHC background genes on the induction of CD4+T cells that prevent rejection of a highly immunogenic tumor,FBL-3." Int.Immunol.6. 839-846 (1994)

[文献書誌] Kobayashi.Y.,et.al.: "Expression and function of multidrug resistance P-glycoprotein in a cultured natural killer cell-rich population revealed by MRK16 monoclonal antibody and AHC-52." Biocem.Pharmacol.48. 1641-1646 (1994)

[文献書誌] watanabe,N.,et.al.: "Selective release of a processed from interleukin 1α." Cytokine. 6. 597-601 (1994)

[文献書誌] Fujiwara,H.,et.al.: "The absence of IgE antibody-mediated augmentation of immune responses in CD23-deficient mice." Proc.Natl.Acad.Sci.UAS. 91. 6835-6839 (1994)

[文献書誌] Ishikawa,Y.,et.al.: "Establishment of lipopolysaccharide-dependent nuclear factor-kB activation in a cell-free system." J.Biol.Chem.270. 4158-4164 (1995)

[文献書誌] Kishimoto,T.,et.al.: "Cytokine signal transduction." Cell. 76. 253-262 (1994)

[文献書誌] Akira,S.,et.al.: "Molecular cloning of APRF,a novel IFN-Stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway" Cell. 71. 63-71 (1994)

[文献書誌] Tanaka,T.,et.al.: "Targeted disruption of the NF-IL6 gene discloses its essential role in bacteria killing and tumor cytotoxicity by macrophages." Cell. (in press). (1995)

[文献書誌] 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.120. 279-285 (1994)

[文献書誌] Mizuhara,H.,et.al.: "T cell activation associated hepatic injury:Mediation by tumor necrosis factor and protection by interleukin-6." J.Exp.Med.179. 1529-1537 (1994)

[文献書誌] Kawabe,T.,et.al.: "Immunoglobulin class switching and germinal center formation are impaired in CD40-deficient mice." Immunity. 1. 167-178 (1994)

[文献書誌] Tsuruta,R.,et.al.: "cAMP inhibits expression of the IL-2 gene through the NF-AT sequence and transfection of NF-AT cDNAs abrogates the sensitivity of EL-4 cells to cAMP." J.Immunol.(in press).

[文献書誌] Kinoshita,T.,et.al.: "Suppression of apoptotic death in hematopoietic cells by signaling through the IL-3/GM-CSF receptors." EMBO J.14. 266-275 (1995)

[文献書誌] Nabioullin,R.,et.al.: "Induction mechanism of human blood CD8+T cell proliferation and cytotoxicity by natural killer cell stimulatory factor(interleukin-12)." Jpn.J.Cancer.Res.86. 853-861 (1994)

[文献書誌] Haku,T.,et.al.: "Human alveolar macrophages augment natural killer cell stimulatory factor(interleukin-12)-inducible killer actibity from autologous blood lymphocytes." Jpn.J.Cancer.Res.86. 81-87 (1995)

[文献書誌] Yano,S.,et.al.: "Differential effects of anti-inflammatory cytokines(IL-4,IL-10 and IL-13)on tumoricidal.and chemotactic properties of human monocytes induced by monocyte chemotactic and activating factor." J.Leukoc.Biol.(in press).

[文献書誌] Takeuchi,A.,et.al.: "Purification and Characterization of a Human Erythrocyte-derived Growth Factor with a Wide Target Cell Spectrum." J.Biol.Chem.269. 24935-24940 (1994)

[文献書誌] Takeuchi,A.,et.al.: "A human erthrocyte-derived growth promoting factor with a wide target cell spectrum:Identification as catalase." Cancer Res.(in press). (1995)

[文献書誌] Watanabe,S.,et.al.: "Regulation by dietary essential fatty acid balance of tumor necrosis factor production in mouse macrophages." J.Leukoc.Biol.53. 151-156 (1993)

[文献書誌] Watanabe,S.,et.al.: "Regulation by lipopolysaccharaide-induced tumor necrosis α factor production by endogenous prostaglandin E2 in rat resident and thioglycollate-elicited macrophage." J.Lipid.Mediat.10. 283-294 (1994)

1994 年度実績報告書

松島綱治金沢大学, がん研究所, 教授 (50222427)