1999 年度実績報告書

転写因子NF-κBに関する基礎的研究とシグナル・トランスダクション療法

研究課題

研究課題/領域番号	10557052
研究機関	名古屋市立大学
研究代表者	岡本尚名古屋市立大学, 医学部, 教授 (40146600)
研究分担者	手塚俊文名古屋市立大学, 医学部, 助手河邊拓己名古屋市立大学, 医学部, 助手 (30224843)
キーワード	NF-κB / 転写 / 炎症免疫応答 / コンプレッサー / アポトーシス / AIDS / 慢性関節リウマチ / がん
研究概要	NF-κB(nuclear factor kappa B)は、免疫・炎症反応に関わる遺伝子群やエイズウイルスの増殖を転写レベルで制御する転写因子であり、慢性関節リウマチを始めとする免疫・アレルギー疾患や後天性免疫不全症候群(AIDS)などの病態への関与が示唆される。また、NF-κBにはプログラム細胞死(apoptosis)を抑制する作用もあることから、発癌過程とその進展にも関与すると考えられている。我々は、これらのカテゴリーの異なる疾患がNF-κBという共通の分子基盤を持つことに注目した。そこで、NF-κBの多彩な生物学的作用とNF-κB自体の制御に関わるメカニズムを明らかにするために、分子生物学的および生化学的研究に加え最近ではプロテオミクス的方法論も含めて一貫した基礎研究を展開してきた。その結果以下の事実を明らかにした。 (1)NF-κBの活性化過程に関わる新たなシグナル伝達系(新規リン酸化酵素とレドックス調節機構)の同定。 (2)NF-κBによるアポトーシス抑制作用の分子機構の解明。 (3)NF-κBの転写活性化作用を抑制する作用を持つ新たなコレプレッサー蛋白とその遺伝子(RelA-associated inhibitorとGroucho-related genes)の分離・同定。これらの成果をもとに、悪性腫瘍の進展および転移の抑制、AIDSウイルス増殖制御、および慢性関節リウマチの新たな治療戦略、など臨床への応用を追求している。

研究成果
(22件)

すべてその他

すべて文献書誌 (22件)

[文献書誌] Saliou,C.: "Antioxidants modulate acute solar ultraviolet radiation-induced NF-kappa-B activation in a human keratinocyte cell line"Free Radic. Biol. Med.. 26. 174-183 (1999)
[文献書誌] Asamitsu,K.: "Alteration of the cellular response to interleuklin 1β by SV40 large T antigen in rheumatoid synovial fibroblasts"Arch. Virol.. 144. 317-327 (1999)
[文献書誌] Traber,E.K.: "Anti-rheumatic compound aurothioglucose inhibits tumor necrosis factor-α-induced HIV-1 replication in latently infected OM10.1 and Ach2 cells"Int. Immunol.. 11. 143-150 (1999)
[文献書誌] Yoshida,S.: "Inhibition of IL-6 and IL-8 induction from the cultured rheumatoid synovial fibroblasts by treatment with aurothioglucose"Int. Immunol.. 11. 151-158 (1999)
[文献書誌] Okamoto,M.: "Inhibition of human immunodeficiency virus type 1 replication by combination of transcription inhibitor K-12 and other antiretroviral agents in acutely and chronically infected cells"Antimicrob. Agents. Chemother.. 43. 492-497 (1999)
[文献書誌] Yang,J.-P: "Identification of a novel inhibitor of nuclear Factor-kB,RelA-associated inhibitor"J. Biol. Chem.. 274. 15662-15670 (1999)
[文献書誌] Yang,J.-P: "NF-kB subunit p65 binds to 53BP2 and inhibits cell death induced by 53BP2"Oncogene.. 18. 5177-5186 (1999)
[文献書誌] Takahashi,N: "Genetic heterogeneity of the immunogenic viral capsid protein region of human parvovirus B19 isolates obtained from a single outbreak in a paediatric ward"FEBS Lett.. 450. 289-293 (1999)
[文献書誌] Goto,D.: "Tublar morphogenesis by genotoxic therapeutic agents that induce NF-kB activation in human vascular endothelial cells"Angiogenesis. 2. 345-356 (1999)
[文献書誌] Yoshida,S.: "Involvement of Thioredoxin in rheumatoid Arghritis: Its co-stimulatory roles in the TNF-α-induced production of IL-6 and IL-8 from cultured synovial fibroblasts"J. Immunol.. 163. 351-358 (1999)
[文献書誌] Maurice,M.M.: "Expression of The thioredoxin-thioredox reductase system in the inflamed joints of patients with rtheumatoid arthritis"Arthritis Rheum. 42. 2430-2439 (1999)
[文献書誌] Asamitsu,K.: "Conservation of the central proline-rich (PxxP) motifs of human immunodeficiency virus type 1 Nef protein during the disease progression in two hemophiliac patients"FEBS Lett.. 459. 399-404 (1999)
[文献書誌] Suganuma,M.: "Sensitization of cencer cell to DNA damage-induced cell death by specific cell cycle G2 checkpoint abrogation"Cancer Res.. 59. 5887-5891 (1999)
[文献書誌] Sakaguchi,T.: "Participation of platelet-activating factor in the lipopolysaccharide-induced liver injury in partially hepatectomized rats"Hepatology. 30. 959-967 (1999)
[文献書誌] Suzuki,M: "The role of p38 mitogen-activated protein kinase in IL-6 and IL-8 production from the TNF-α or IL-1β stimulated rheumatoid synovial fibroblasts"FEBS Lett.. 465. 23-27 (2000)
[文献書誌] Mori,T: "Aberrant overxpression of 53BP2 mRNA in lung cancer cell lines"FEBS Lett.. 465. 124-128 (2000)
[文献書誌] Tetsuka,T: "Inhibition of nuclear facter-κB-mediated transcription by association with the amino-terminal rnhancer of split (AES) a groucho-related protein lacking WD40 repeats"J. Biol. Chem.. 275. 4383-4390 (2000)
[文献書誌] Kameoka,M: "Evidence for Regulation of NF-κB by Poly (ADP-ribose) Polymerase"Biochem. J.. (in press).
[文献書誌] Kajino,S.: "Evidence that de novo protein synthesis is dispensable for anti-apoptotic effects of NF-κB"Ouncogene.. (in press).
[文献書誌] Kanazawa,S.: "Tat competes with CIITA for the binding to P-TEFb and blocks the expression of MHC class II genes in HIV infection"Immunity.. 12. 61-70 (2000)
[文献書誌] Okamoto,H: "HIV-1 replication is inhibited by a pseudo-substrate peptide that blocks Tat transactivation"J. Viol.. (in press).
[文献書誌] Okamoto,T: "Role of thioredoxin in the redox regulation of gene expression in inflammatory diseases. Free radicals and inflammation."Birkhauser Verlag Basel. 259 (2000)

1999 年度 実績報告書

転写因子NF-κBに関する基礎的研究とシグナル・トランスダクション療法

研究代表者

岡本 尚 名古屋市立大学, 医学部, 教授 (40146600)

研究成果

[文献書誌] Saliou,C.: "Antioxidants modulate acute solar ultraviolet radiation-induced NF-kappa-B activation in a human keratinocyte cell line"Free Radic. Biol. Med.. 26. 174-183 (1999)

[文献書誌] Asamitsu,K.: "Alteration of the cellular response to interleuklin 1β by SV40 large T antigen in rheumatoid synovial fibroblasts"Arch. Virol.. 144. 317-327 (1999)

[文献書誌] Traber,E.K.: "Anti-rheumatic compound aurothioglucose inhibits tumor necrosis factor-α-induced HIV-1 replication in latently infected OM10.1 and Ach2 cells"Int. Immunol.. 11. 143-150 (1999)

[文献書誌] Yoshida,S.: "Inhibition of IL-6 and IL-8 induction from the cultured rheumatoid synovial fibroblasts by treatment with aurothioglucose"Int. Immunol.. 11. 151-158 (1999)

[文献書誌] Okamoto,M.: "Inhibition of human immunodeficiency virus type 1 replication by combination of transcription inhibitor K-12 and other antiretroviral agents in acutely and chronically infected cells"Antimicrob. Agents. Chemother.. 43. 492-497 (1999)

[文献書誌] Yang,J.-P: "Identification of a novel inhibitor of nuclear Factor-kB,RelA-associated inhibitor"J. Biol. Chem.. 274. 15662-15670 (1999)

[文献書誌] Yang,J.-P: "NF-kB subunit p65 binds to 53BP2 and inhibits cell death induced by 53BP2"Oncogene.. 18. 5177-5186 (1999)

[文献書誌] Takahashi,N: "Genetic heterogeneity of the immunogenic viral capsid protein region of human parvovirus B19 isolates obtained from a single outbreak in a paediatric ward"FEBS Lett.. 450. 289-293 (1999)

[文献書誌] Goto,D.: "Tublar morphogenesis by genotoxic therapeutic agents that induce NF-kB activation in human vascular endothelial cells"Angiogenesis. 2. 345-356 (1999)

[文献書誌] Yoshida,S.: "Involvement of Thioredoxin in rheumatoid Arghritis: Its co-stimulatory roles in the TNF-α-induced production of IL-6 and IL-8 from cultured synovial fibroblasts"J. Immunol.. 163. 351-358 (1999)

[文献書誌] Maurice,M.M.: "Expression of The thioredoxin-thioredox reductase system in the inflamed joints of patients with rtheumatoid arthritis"Arthritis Rheum. 42. 2430-2439 (1999)

[文献書誌] Asamitsu,K.: "Conservation of the central proline-rich (PxxP) motifs of human immunodeficiency virus type 1 Nef protein during the disease progression in two hemophiliac patients"FEBS Lett.. 459. 399-404 (1999)

[文献書誌] Suganuma,M.: "Sensitization of cencer cell to DNA damage-induced cell death by specific cell cycle G2 checkpoint abrogation"Cancer Res.. 59. 5887-5891 (1999)

[文献書誌] Sakaguchi,T.: "Participation of platelet-activating factor in the lipopolysaccharide-induced liver injury in partially hepatectomized rats"Hepatology. 30. 959-967 (1999)

[文献書誌] Suzuki,M: "The role of p38 mitogen-activated protein kinase in IL-6 and IL-8 production from the TNF-α or IL-1β stimulated rheumatoid synovial fibroblasts"FEBS Lett.. 465. 23-27 (2000)

[文献書誌] Mori,T: "Aberrant overxpression of 53BP2 mRNA in lung cancer cell lines"FEBS Lett.. 465. 124-128 (2000)

[文献書誌] Tetsuka,T: "Inhibition of nuclear facter-κB-mediated transcription by association with the amino-terminal rnhancer of split (AES) a groucho-related protein lacking WD40 repeats"J. Biol. Chem.. 275. 4383-4390 (2000)

[文献書誌] Kameoka,M: "Evidence for Regulation of NF-κB by Poly (ADP-ribose) Polymerase"Biochem. J.. (in press).

[文献書誌] Kajino,S.: "Evidence that de novo protein synthesis is dispensable for anti-apoptotic effects of NF-κB"Ouncogene.. (in press).

[文献書誌] Kanazawa,S.: "Tat competes with CIITA for the binding to P-TEFb and blocks the expression of MHC class II genes in HIV infection"Immunity.. 12. 61-70 (2000)

[文献書誌] Okamoto,H: "HIV-1 replication is inhibited by a pseudo-substrate peptide that blocks Tat transactivation"J. Viol.. (in press).

[文献書誌] Okamoto,T: "Role of thioredoxin in the redox regulation of gene expression in inflammatory diseases. Free radicals and inflammation."Birkhauser Verlag Basel. 259 (2000)

1999 年度実績報告書

岡本尚名古屋市立大学, 医学部, 教授 (40146600)