Mechanism of breakdown of blood-brain barrier accompanied with viral encephalopathy

• Project/Area Number: 20591228
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Nagoya City University
• Principal Investigator: ASAI Kiyofumi Nagoya City University, 大学院・医学研究科, 教授 (70212462)
• Co-Investigator(Kenkyū-buntansha): AOYAMA Mineyoshi 名古屋市立大学, 大学院・医学研究科, 講師 (70363918)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 急性脳症 / 血液脳関門 / アストロサイト / 血管内皮細胞 / サイトカイン

Research Abstract

We have tried to establish immortalized mouse brain endothelial cell lines and rat astrocytes cell line for the co-culture system of both cells. Primary cultured mouse brain endothelial cells were transfected with SV40 T-antigen expressing vector and selected by zeocin and blasticidin. Primary cultured rat astrocytes were transfected with same vectors and selected by some procedures. Three colonies from endothelial cells and 10 colonies from astrocytes were obtained, but in all of the immortalized cell lines, expression of SV40 T was not controlled by tetracycline. Thus Tet-repressor expressing vector was re-transfected to the cell lines and finally 3 astrocyte cell lines were obtained in which expression of SV40 T was controlled by tetracycline. Now we are investigating whether the expression of GFAP changes or not by on/off of SV40 T, and trying to establish co-culture system of endothelial cell lines and astrocyte cell lines.

Research Products

• [Journal Article] FK506 inhibition of gliostatin/thymidine Phosphorylase production induced by tumor necrosis factor-alpha in rheumatoid fibroblasst-like synoviocytes. (2011)
  • Author(s): Yamagami, T.
  • Journal Title: Rheumatol Int Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] FK506 inhibition of gliostatin/thymidine phosphorylase production induced by tumor necrosis factor-alpha in rheumatoid fibroblast-like synoviocytes. (2010)
  • Author(s): Yamagami, T., Waguri-Nagaya, Y., Ikuta, K., Aoyama, M., Asai, K., Otsuka, T.
  • Journal Title: Rheumatol Int in press
  • Peer Reviewed
• [Journal Article] TNF-alpha-induced aquaporin 9 in synoviocytes from patients with OA and RA. (2010)
  • Author(s): Nagahara, M., Waguri-Nagaya, Y., Yamagami, T., Aoyama, M., Tada, T., Inoue, K., Asai, K., Otsuka, T.
  • Journal Title: Rheumatology 49:5 Pages: 898-906
  • Peer Reviewed
• [Journal Article] Resistance to chemotherapeutic agents and promotion of transforming activity mediated by embryonic stem cell-expressed Ras (ERas) signal in neuroblastoma cells. (2010)
  • Author(s): Aoyama, M., Kataoka, H., Kubota, E., Tada, T., Asai, K.
  • Journal Title: Int J Oncol 37:4 Pages: 1011-1016
  • Peer Reviewed
• [Journal Article] Role of ES cell-expressed Ras (ERas) in tumorigenicity of gastric cancer. (2010)
  • Author(s): Kubota, E., Kataoka, H., Aoyama, M., Mizoshita, T., Mori, Y., Shimura, T., Tanaka, M., Sasaki, M., Takahashi, S., Asai, K., Joh, T.
  • Journal Title: Am J Pathol 177:2 Pages: 955-963
  • Peer Reviewed
• [Journal Article] Tranilast suppresses prostate cancer growth and osteoclast differentiation in vivo and in vitro. (2010)
  • Author(s): Sato, S., Takahashi, S., Asamoto, M., Naiki, T., Naiki-Ito, A., Asai, K., Shirai, T.
  • Journal Title: Prostate 70:3 Pages: 229-238
  • Peer Reviewed
• [Journal Article] Contribution of K(ir)2 potassium channels to ATP-induced cell death in brain capillary endothelial cells and reconstructed HEK293 cell model. (2010)
  • Author(s): Yamazaki, D.
  • Journal Title: Am J Physiol Cell Physiol Volume: 300
  • Peer Reviewed
• [Journal Article] TNF-alpha-induced aquaporin 9 in synoviocytes from patients with OA and RA. (2010)
  • Author(s): Nagahara, M.
  • Journal Title: Rheumatology Volume: 49 Pages: 898-906
  • Peer Reviewed
• [Journal Article] Resistance to chemotherapeutic agents and promotion of transforming activity mediated by embryonic stem cell-expressedRas (ERas) signal in neuroblastoma cells. (2010)
  • Author(s): Aoyama, M.
  • Journal Title: Int J Oncol Volume: 37 Pages: 1011-1016
  • Peer Reviewed
• [Journal Article] Role of ES cell-expressed Ras (ERas) in tumorigenicity of gastric cancer. (2010)
  • Author(s): Kubota, E.
  • Journal Title: Am J Pathol Volume: 17 Pages: 955-963
  • Peer Reviewed
• [Journal Article] Tranilast suppresses prostate cancer growth and osteoclast differentiation in vivo and in vitro. (2010)
  • Author(s): Sato, S.
  • Journal Title: Prostate Volume: 3 Pages: 229-238
  • Peer Reviewed
• [Journal Article] The ZFHX3 (ATBF1) transcription factor induces PDGFRB, which activates ATM in the cytoplasm to protect cerebellar neurons from oxidative stress. (2010)
  • Author(s): Kim, T.S.
  • Journal Title: Dis Model Mech Volume: 3 Pages: 752-762
  • Peer Reviewed
• [Journal Article] Tumor suppressor, AT motif binding factor 1 (ATBF1), translocates to the nucleus with runt domain transcription factor 3 (RUNX3) in response to TGF-beta signal transduction. (2010)
  • Author(s): Mabuchi, M.
  • Journal Title: Biochem Biophys Res Commun Pages: 321-325
  • Peer Reviewed
• [Journal Article] Tranilast suppresses prostate cancer growth and osteoclast differentiation in vivo and in vitro (2010)
  • Author(s): Sato, S.
  • Journal Title: Prostate 70 Pages: 229-238
  • Peer Reviewed
• [Journal Article] Prolonged exposure to ammonia increases extracellular glutamate in cultured rat astrocytes. (2009)
  • Author(s): Ohara, K., Aoyama, M., Fujita, M., Sobue, K., Asai, K.
  • Journal Title: Neurosci Lett 462:2 Pages: 109-112
  • Peer Reviewed
• [Journal Article] IGF2 modulates the microenvironment for osteoclastogenesis. (2009)
  • Author(s): Nakao, K., Aoyama, M., Fukuoka, H., Fujita, M., Miyazawa, K., Asai, K., Goto, S.
  • Journal Title: Biochem Biophys Res Commun 378 Pages: 462-466
  • Peer Reviewed
• [Journal Article] Diclofenac enhances proinflammatory cytokine-induced nitric oxide production through NF-kappaB signaling in cultured astrocytes (2009)
  • Author(s): Kakita, H.
  • Journal Title: Toxicol Appl Pharmacol 238 Pages: 56-63
  • Peer Reviewed
• [Journal Article] Prolonged exposure to ammonia increases extracellular glutamate in cultured rat astrocytes (2009)
  • Author(s): Ohara, K.
  • Journal Title: Neurosci Lett 462 Pages: 109-112
  • Peer Reviewed
• [Journal Article] Glucagon-like peptide-1(GLP-1)protects against methylglyoxal-induced PC12 cell apoptosis through the PI3K/Akt/mTOR/GCLc/redox signaling pathway (2009)
  • Author(s): Kimura, R.
  • Journal Title: Neuroscience 162 Pages: 1212-1219
  • Peer Reviewed
• [Journal Article] Diclofenac enhances proinflammatory cytokine-induced nitric oxide productionthrough NF-kB signaling in cultured astrocytes. (2009)
  • Author(s): Kakita, H.
  • Journal Title: Toxicology and Applied Pharmacology in press
  • Peer Reviewed
• [Journal Article] IGF2 modulates the microenvironment for osteoclastogenesis. (2009)
  • Author(s): Nakao, K.
  • Journal Title: Biochem Biophys Res Commun 378 Pages: 462-466
  • Peer Reviewed
• [Journal Article] Localization of reversion-induced LIM protein (RIL) in the rat central nervous system. (2009)
  • Author(s): Iida, Y.
  • Journal Title: Acta Histochem Cytochem 42 Pages: 9-14
  • Peer Reviewed
• [Journal Article] Transforming growth factor-beta signaling at the tumor-bone interface promotes mammary tumor growth and osteoclast (2009)
  • Author(s): Futakuchi, M.
  • Journal Title: Cancer Sci 100 Pages: 71-81
  • Peer Reviewed
• [Journal Article] Severity of virilization of external genitalia in Japanese patients with salt-wasting 21-hydroxylase deficiency. (2008)
  • Author(s): Sugiyama, Y., Mizuno, H., Hayashi, Y., Imamine, H., Ito, T., Kato, I., Yamamoto-Tomita, M., Aoyama, M., Asai, K., Togari, H.
  • Journal Title: Tohoku J Exp Med 215:4 Pages: 341-348
  • NAID: 10021951345
  • Peer Reviewed
• [Journal Article] Lactic acid increases aquaporin 4 expression on the cell membrane of cultured rat astrocytes. (2008)
  • Author(s): Morishima, T., Aoyama, M., Iida, Y., Yamamoto, N., Hirate, H., Arima, H., Fujita, Y., Sasano, H., Tsuda, T., Katsuya, H., Asai, K., Sobue, K.
  • Journal Title: Neurosci Res 61 Pages: 18-26
  • Peer Reviewed
• [Journal Article] Transforming growth factor beta derived from bone matrix promotes cell proliferation of prostate cancer and osteoclast activation-associated osteolvsis in the bone microenvironment. (2008)
  • Author(s): Sato, S.
  • Journal Title: Cancer Sci 99 Pages: 316-323
  • Peer Reviewed
• [Journal Article] Severity of virilization of external genitalia in Japanese patients with salt-wasting 21-hydroxylase deficiency. (2008)
  • Author(s): Sugiyama, Y.
  • Journal Title: Tohoku J Exp Med 215 Pages: 341-348
  • Peer Reviewed
• [Journal Article] Lactic acid increases aquaporin 4 expression on the cell membrane of cultured rat astrocytes. (2008)
  • Author(s): Morishima, T.
  • Journal Title: Neurosci Res 61 Pages: 18-26
  • Peer Reviewed
• [Presentation] アストロサイト由来エリスロポエチンがオリゴデンドロサイト前駆細胞に与える影響 (2010)
  • Author(s): 青山峰芳
  • Organizer: 第15回グリア研究会
  • Place of Presentation: 九州大学医学部百年講堂大ホール(福岡県)
  • Year and Date: 2010-10-23
• [Presentation] The ZHFX3/ATBF1 transcription factor transduces ATM signaling to regulate PDGF receptor beta and protect cerebellar neurons from oxidative stress. (2010)
  • Author(s): Nan GAO, Tae-sum Kim, Mitsuko Suzuki, Makoto Kawaguchi, Cha-Gyum Jung, Kiyofumi Asai, Yutaka Miura
  • Organizer: BMB2010(第33回日本分子生物学会年会、第83回日本生化学会大会合同大会)
  • Place of Presentation: 神戸
• [Presentation] 抗TNF 阻害剤にて治療した関節リウマチ患者の血清グリオスタチン濃度の推移 (2010)
  • Author(s): 永谷祐子、山上貴也、生田憲史、青山峰芳、浅井清文、大塚隆信
  • Organizer: 第83回日本整形外科学会学術総会
  • Place of Presentation: 東京
• [Presentation] 抗TNF阻害剤を使用した関節リウマチ患者の血清グリオスタチン濃度の12カ月間の推移 (2010)
  • Author(s): 生田憲史、永谷祐子、山上貴也、青山峰芳、浅井清文、大塚隆信
  • Organizer: 第54回日本リウマチ学会総会・学術集会/第19回国際リウマチシンポジウム
  • Place of Presentation: 神戸
• [Presentation] 敗血症におけるastrocyteでのHIF (hypoxia inducible factor)-1αの役割 (2010)
  • Author(s): 高柳猛彦、箕輪堯久、秋吉瑠美子、太田晴子、徐民恵、水落雄一郎、幸村英文、藤田義人、笹野寛、浅井清文、祖父江和哉
  • Organizer: 第37回日本集中治療医学会
  • Place of Presentation: 広島
• [Presentation] 培養アストロサイトへの長期アンモニア刺激による細胞外グルタミン酸の上昇 (2010)
  • Author(s): 青山峰芳
  • Organizer: Neuro 2010
  • Place of Presentation: 神戸コンベンションセンター(兵庫県)
• [Presentation] 抗TNF阻害剤を使用した関節リウマチ患者の血清グリオスタチン濃度の12カ月間の推移 (2010)
  • Author(s): 生田憲史
  • Organizer: 第54回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸ポートピアホテル(兵庫県)
• [Presentation] 抗TNF阻害剤にて治療した関節リウマチ患者の血清グリオスタチン濃度の推移 (2010)
  • Author(s): 永谷祐子
  • Organizer: 第83回日本整形外科学会学術総会
  • Place of Presentation: 東京国際フォーラム(東京都)
• [Presentation] The ZHFX3/ATBF1 transcription factor transducer ATM signaling to regulate PDGF receptor beta and protect cerebellar neurons from oxidative stress. (2010)
  • Author(s): Nan GAO
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
• [Presentation] 敗血症における astrocyte でのHIF(hypoxia inducible factor)-1αの役割 (2010)
  • Author(s): 高柳猛彦
  • Organizer: 第37回日本集中治療医学会
  • Place of Presentation: 広島
• [Presentation] ジクロフェナックナトリウムがアストロサイトのNO産生に及ぼす影響-インフルエンザ感染に伴う脳症悪化のメカニズム- (2009)
  • Author(s): 青山峰芳、垣田博樹、加藤晋、戸苅創、浅井清文
  • Organizer: 第14回グリア研究会
  • Place of Presentation: 大阪
  • Year and Date: 2009-11-14
• [Presentation] ATMの活性化シグナルはZFHX3(ATBF1)の転写活性化を介して小脳ニューロンの生存に寄与するPDGFRB発現誘導を誘導する(Asignal link ATM with ZFHX3 (ATBF1) indices PDGF Reseptor bete for protein of cerebellar neurons.) (2009)
  • Author(s): 金泰善、川口誠、浅井清文、三浦裕
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] TNF-αは線維芽腫細胞様滑膜細胞においてアクアポリン9の発現を誘導する (2009)
  • Author(s): 長原正静、永谷祐子、山上貴也、青山峰芳、多田豊曠、浅井清文、大塚隆信
  • Organizer: 第24回日本整形科学会基礎学術集会
  • Place of Presentation: 横浜
• [Presentation] ジクロフェナックがサイトカイン刺激によってアストロサイトから誘導されるNO産生を増強する-インフルエンザ脳症増悪化メカニズムの解析- (2009)
  • Author(s): 青山峰芳、垣田博樹、フセインモハメド、加藤晋、鈴木悟、伊藤哲也、戸苅創、浅井清文
  • Organizer: 第52回日本神経化学会(伊香保)大会
  • Place of Presentation: 伊香保
• [Presentation] 炎症性サイトカインとCOX阻害剤がアストロサイトのNOx産生に及ぼす影響 (2009)
  • Author(s): 垣田博樹、青山峰芳、加藤晋、鈴木悟、戸苅創、浅井清文
  • Organizer: 第112回日本小児科学会学術集会
  • Place of Presentation: 奈良
• [Presentation] 黒霊芝の神経成長因子産生及び神経突起伸展促進作用 (2009)
  • Author(s): 當銘一文、小林信彦、石井泉、田中悟、青山峰芳、浅井清文
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
• [Presentation] Differential inflammatory gene expression in young and middle aged mice during injury-induced hippocampal neurogenesis. (2009)
  • Author(s): McPherson C.A., Aoyama M., Grissom S.F., Gohlke J., Harry G.J.
  • Organizer: The American Society for Neurochemistry 40th Annual Meeting
  • Place of Presentation: Charleston, SC, USA
• [Presentation] TNF-αは線維芽腫細胞様滑膜細胞においてアクアポリン9の発現を誘導する (2009)
  • Author(s): 長原正静
  • Organizer: 第24回日本整形科学学会基礎学術集会
  • Place of Presentation: 横浜
• [Presentation] ATMの活性化シグナルはZFHX3(ATBF1)の転写活性化を介して小脳ニューロンの生存に寄与するPDGFRB発現誘導を誘導する (2009)
  • Author(s): 金泰善
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] 関節リウマチ、変形性関節症の滑膜組織におけるアクアポリンの発現 (2008)
  • Author(s): 長原正静、永谷祐子、山上貴也、青山峰芳、多田豊曠、浅井清文、大塚隆信
  • Organizer: 第59回名古屋市立大学医学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-12-07
• [Presentation] アストロサイトの脳内部位特異性の解析 (2008)
  • Author(s): 青山峰芳、垣田博樹、加藤晋、藤田政隆、祖父江和哉、浅井清文
  • Organizer: 第13回グリア研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-08
• [Presentation] アストロサイトの脳内部位特異性の解析 (2008)
  • Author(s): 青山峰芳
  • Organizer: 第13回クリア研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-08
• [Presentation] P19細胞の神経分化誘における転写調節因子ATBF1による細胞外マトリックス接着関連因子の発現調節 (2008)
  • Author(s): 三浦裕、金泰善、鈴木光子、川口誠、鄭且均、浅井清文
  • Organizer: 第31回日本分子生物学会年会(BMB2008)
  • Place of Presentation: 神戸
• [Presentation] Analysis of a BAC transgenic mouse line in adulthood : distribution of genomic recombination by gfap-promotor-derived cre in the brain. (2008)
  • Author(s): Fujita M., Ogasawara O.,Tanaka M., Aoyama M., Iwasato T., Asai K., Yamada K., Itohara, S.
  • Organizer: Neuroscience 2008, the Society for Neuroscience's 38th annual meeting
  • Place of Presentation: Washington, DC, U.S.A
• [Presentation] Region-specific expression of a water nervous system. (2008)
  • Author(s): 青山峰芳, 垣田博樹, 加藤晋, 藤田政隆, 祖父江和哉, 浅井清文
  • Organizer: Neuroscience 2008, the Society for Neuroscience's 38th annual meeting
  • Place of Presentation: Washington, DC, U.S.A.
• [Presentation] 新規Ras遺伝子、Erasの胃癌転移における役割(Novel Eras plays crucial role for epithelial to mesenchymal transition and liver metastases in human gastric cancer) (2008)
  • Author(s): 久保田英嗣、片岡洋望、佐々木誠人、小笠原尚高、志村貴也、溝下勤、平田慶和、浅井清文、城卓志
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 関節水症におけるアクアポリン発現の検討 (2008)
  • Author(s): 長原正静、永谷祐子、山上貴也、青山峰芳、浅井清文、多田豊曠、大塚隆信
  • Organizer: 第23回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都
• [Presentation] FK506はリウマチ由来線維芽細胞様滑膜細胞においてgliostatin産生を抑制する (2008)
  • Author(s): 山上貴也、永谷祐子、長原正静、青山峰芳、浅井清文、大塚隆信
  • Organizer: 第23回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都
• [Presentation] カオリン水頭症モデルラットにおけるアクアポリン発現に関しての検討 (2008)
  • Author(s): 藤田政隆、間瀬光人、磯村健一、青山峰芳、浅井清文、山田和雄
  • Organizer: 日本脳神経外科学会第67回学術総会
  • Place of Presentation: 盛岡
• [Presentation] アストロサイトの部位特異性に関わる分子の同定(Identification of the molecules, which are responsible for astrological heterogeneity in the central nervous system) (2008)
  • Author(s): 青山峰芳、垣田博樹、加藤晋、藤田政隆、祖父江和哉、浅井清文
  • Organizer: 第51回日本神経化学会大会
  • Place of Presentation: 富山
• [Presentation] 乳酸アシドーシスは水チャネル<アクアポリン>のアストロサイト細胞膜への集積を促進する(Lactic acid increases aquporin 4 expression on the cell membrane of cultured rat astrocytes). (2008)
  • Author(s): 祖父江和哉、森島徹朗、青山峰芳、高柳猛彦、浅井清文
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
• [Presentation] GFAP及びAQP4プロモーターを用いたCreトランスジェニックマウスの解析(Analysis of transgenic mice of Cre recombinase derived from GFAP or AQP4 promotor). (2008)
  • Author(s): 藤田政隆、小笠原治、田中三佳、矢口邦雄、岩里琢治、浅井清文、山田和雄
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
• [Presentation] 変形性関節症および関節リウマチの滑膜組織におけるアクアポリンの発現(Expression of aquaporin in synovial tissue of osteoarthritis and rheumatoidarthritis). (2008)
  • Author(s): 長原正静、永谷祐子、山上貴也、青山峰芳、浅井清文、大塚隆信
  • Organizer: リウマチ学会2008(第52回日本リウマチ学会総会・学術集会)
  • Place of Presentation: 札幌
• [Presentation] Analysis of a BAC transgenic mouse line in adulthood : distribution of genomic recombination by gfap-promotor-derived cre in the brain. (2008)
  • Author(s): Fujita, M.
  • Organizer: Neuroscience 2008, the Society for Neuroscience's 38th annual meeting
  • Place of Presentation: Washington, DC, U.S.A.
• [Presentation] Identification of the molecules, which are responsible for astrological heterogeneity in the central nervous system (2008)
  • Author(s): 青山峰芳
  • Organizer: 第51回日本神経化学会大会
  • Place of Presentation: 富山
• [Presentation] Expression of aquaporin in synovial tissue of osteoarthritis andrheumatoid arthritis. (2008)
  • Author(s): 長原正静
  • Organizer: 第52回日本リウマチ学会総会・学術集会
  • Place of Presentation: 札幌
• [Presentation] Lactic acid increases aquporin 4 expression on the cell membrane of cultured rat astrocytes. (2008)
  • Author(s): 祖父江和哉
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
• [Presentation] Analysis of transgenic mice of Cre recombinase derived from GFAP or AQP4 promotor. (2008)
  • Author(s): 藤田政隆
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
• [Presentation] FK506 はリウマチ由来線維芽細胞様滑膜細胞においてgliostatin産生を抑制する (2008)
  • Author(s): 山上貴也
  • Organizer: 第23回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都
• [Presentation] Novel Eras plays crucial role for epithelial to mesenchymal transition and liver metastases in human gastric cancer. (2008)
  • Author(s): 久保田英嗣
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] P19 細胞の神経分化誘における転写調節因子ATBF1による細胞外マトリックス接着関連因子の発現調節 (2008)
  • Author(s): 三浦 裕
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸