Effect of BDNF on proliferation of leukemic cells and application to the treatment.

• Project/Area Number: 19591147
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: YOSHIDA Yasuhiro University of Occupational and Environmental Health, Japan, 医学部, 准教授 (10309958)
• Co-Investigator(Kenkyū-buntansha): TSUKADA Junichi 産業医科大学, 医学部, 准教授 (20227367) ; OKADA Kazumasa 産業医科大学, 医学部, 助教 (30341499)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 白血病 / BDNF / マクロファージ / サイトカイン / Treg

Research Abstract

申請者は神経栄養因子の一つであるBDNFが白血病細胞株より恒常的に産生されていることを見出した。BDNFは免疫細胞(例えばマクロファージなど)のはたらきを抑制することで、白血病細胞が増殖しやすい環境を整えていることがわかった。特にCD3によりBDNFの受容体であるTrkBが誘導されること、またBDNFにより制御性T細胞が誘導されることは、抗腫瘍効果を考える上で非常に興味深い知見である。

Research Products

• [Journal Article] Effects of 1-bromopropane, a substitute for chlorofluorocarbons, on brain-derived neurotrophic factor (BDNF) expression. (2009)
  • Author(s): Yoshida, Y., Nakano, Y., Ueno, S., Liu, J.Q., Fueta, Y., Ishidao, T., Kunugita, N., Yanagihara, N., Sugiura, T., Yamashita, U., Hori, H.
  • Journal Title: Int ImmPharma 9 Pages: 433-438
  • Peer Reviewed
• [Journal Article] Cucurbitacin D isolated from Trichosanthes kirilowii induces apoptosis in human hepatocellular carcinoma. (2009)
  • Author(s): Takahashi, N., Yoshida, Y., Sugiura, T., Matsuno, K., Fujino, A., Yamashita, U.
  • Journal Title: Int ImmPharma 9 Pages: 508-513
  • Peer Reviewed
• [Journal Article] An indoor air pollutant 2-ethyl-hexanol activates CD4 cells (2009)
  • Author(s): Yoshida, Y., Liu, J.Q., Sugiura, T., Ishitao, T., Ueno, S., Yanagita, H., Fueta, Y., Kunugita, N., Hori, H., Yamashita, U.
  • Journal Title: Chemico-Bio Intera 177 Pages: 137-141
  • Peer Reviewed
• [Journal Article] An indoor air pollutant 2-ethyl-hexanol activates CD4 cells (2009)
  • Author(s): Yoshida, Y., et al.
  • Journal Title: Chemico-Bio Interaction 177 Pages: 137-141
  • Peer Reviewed
• [Journal Article] Effects of 1-bromopropane, a substitute for chlorofluorocarbons, on brain-derived neurotrophic factor (BDNF) expression. (2009)
  • Author(s): Yoshida, Y., et al.
  • Journal Title: Int Immunopharma 9 Pages: 433-438
  • Peer Reviewed
• [Journal Article] Cucucrbitacin D isolated from Trichosanthes kirilowii induces apoptosis in human hepatocellular carcinoma (2009)
  • Author(s): Takahashi, N., et al.
  • Journal Title: Int Immunopharma 9 Pages: 508-513
  • Peer Reviewed
• [Journal Article] DNA-binding activity of NF-kappaB and phosphorylation of p65 are induced by N-acetylcysteine through phosphatidylinositol (PI) 3-kinase. (2008)
  • Author(s): Liu, J., Yoshida, Y. and Yamashita, U.
  • Journal Title: Mol Imm 45 Pages: 3984-3989
  • Peer Reviewed
• [Journal Article] Intracellular HMGB1 transactivates the human IL1B gene promoter through association with an Ets transcription factor PU.1. (2008)
  • Author(s): Mouri, F., Tsukada, J., Mizobe, T., Higashi, T., Yoshida, Y., Minami, Y., Izumi, H., Kominato, Y., Kohno, K., Tanaka, Y.
  • Journal Title: Eur J Heamatology 80 Pages: 10-19
  • Peer Reviewed
• [Journal Article] DNA-binding activity of NF-kappaB and phosphorylation of p65 are in duced by N-acetylcysteine through phosphatidylinositol (PI) 3-kinase. (2008)
  • Author(s): Liu, J. Q, et al.
  • Journal Title: Mol Immunol 45 Pages: 3984-3989
  • Peer Reviewed
• [Journal Article] Arsenic trioxide augments Chk2/p53-mediated apoptosis by inhibiting oncogenic Wip1 phosphatase (2008)
  • Author(s): Yoda, A., et al.
  • Journal Title: J Biol Chem 283 Pages: 18969-973
  • Peer Reviewed
• [Journal Article] Intracellular HMGB1 transactivates the human IL1B gene promoterthrouh association with an Ets transcrition factor PU.1 (2008)
  • Author(s): Mouri, F., et. al.
  • Journal Title: Eur J Heamatology 80 Pages: 10-19
  • Peer Reviewed
• [Journal Article] Constitutive association of MyD88 to IRAK1 in HTLV-1-transformed T-cells. (2007)
  • Author(s): Mizobe, T., Tsukada, J., Higashi, T., Mouri, F., Matsuura, A., Taniguchi, R., Minami, Y., Yoshida, Y., Tanaka, Y.
  • Journal Title: Exp Hematology 38 Pages: 1812-1822
  • Peer Reviewed
• [Journal Article] Suppressive effect of reactive oxygen species on CD40-induced B cell activation. (2007)
  • Author(s): Liu, J., Yoshida, Y. and Yamashita, U.
  • Journal Title: FEBS Lett 581 Pages: 5043-5049
  • Peer Reviewed
• [Journal Article] Phosphorylation of IRF8 in a pre-associated complex with Spi-1/PU.1 and non-phosphorylated Stat1 is critical for LPS induction of the IL1B gene. (2007)
  • Author(s): Unlu, S., Kumar, A., Waterman, WR., Tsukada, J., Wang, KZ., Galson, DL., Auron, PE.
  • Journal Title: Mol Immunol 44 Pages: 3364-3379
  • Peer Reviewed
• [Journal Article] Suppressive effect of reactlve oxygen spccles on CD40-induceu B cell actlvatlon (2007)
  • Author(s): Liu, J., et. al.
  • Journal Title: FEBS Lett 581 Pages: 5043-5049
  • Peer Reviewed
• [Journal Article] Constitutive association of MyD88 to IRAK1 in HTLV-1-transformed T-cells (2007)
  • Author(s): Mizobe, T., et. al.
  • Journal Title: Exp Hematology 38 Pages: 1812-1822
  • Peer Reviewed
• [Journal Article] Phosphorylation of IRF8 in a pre-associated complex with Spi-1/PU.1 and non-phosphorylated Statl is critical for LRS inducion of the IL1B gene (2007)
  • Author(s): Unlu, S., et. al.
  • Journal Title: Mol Immunology 44 Pages: 3364-3379
  • Peer Reviewed
• [Presentation] BDNF attenuated cytokine production and induced FOXP3 in CD4 cells (2008)
  • Author(s): 吉田安宏, 山下優毅
  • Organizer: 第38 回日本免疫学会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-12
• [Presentation] Activation of NF-κB is induced by N-acetylcysteine through phosphatidyl inositol (PI) 3-kinase (2008)
  • Author(s): Yoshida, Y., et al.
  • Organizer: 第31回日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] Activation of NF-kB is induced by N-acetylcysteine through phosphatidyl inositol (PI) 3-kinase (2008)
  • Author(s): 吉田安宏, 劉冀琴, 山下優毅
  • Organizer: 第31回日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-03
• [Presentation] BDNF attenuated cytokine production and induced FOXP3 in CD4 cells (2008)
  • Author(s): Yoshida, Y., et al.
  • Organizer: 第38回日本免疫学会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-03
• [Presentation] A non-phosphorylated STAT1 enhanced LPS-induced NF-kB activation. (2008)
  • Author(s): Yoshida, Y. and Yamashita, U.
  • Organizer: 33rd FEBS Congress and 11th IUMBM Conference
  • Place of Presentation: Athens, Greece
  • Year and Date: 2008-06-29
• [Presentation] A non-phosphorylated STAT1 enhanced LPS-induced NF-κB activation. (2008)
  • Author(s): Yoshida, Y., et al.
  • Organizer: 33^<rd> FEBS Congress and 11th IUMBM Conference
  • Place of Presentation: Athens, Greece
  • Year and Date: 2008-06-29
• [Presentation] TRAF6 C-terminal domain plays an inhibitory role of VEGF gene in leukemic cell line, HUT102 (2007)
  • Author(s): 吉田安宏, 劉冀琴, 山下優毅
  • Organizer: 第30回日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] TRAF6 C-terminal domain plays an inhibitory role of VEGF gene in leukemic cell lile,HUT102 (2007)
  • Author(s): Yoshida, Y, et. al.
  • Organizer: 第30回日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] Cytokine production in macrophage is attenuated by Brain-derived neurotrophic factor (BDNF) produced by leukemia cell (2007)
  • Author(s): 吉田安宏, 劉冀琴, 山下優毅
  • Organizer: 第37回日本免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-22
• [Presentation] Cytokine production in macrophage is attenuated by brain-derivedneurotrophix factor (BDNF)produced by leukemia cell (2007)
  • Author(s): Yoshida, Y., et. al.
  • Organizer: 第37回日本免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-22
• [Presentation] Brain-derived neurotrophic factor (BDNF) produced by leukemia cell attenuated cytokine production in macrophage. (2007)
  • Author(s): Yoshida, Y., Liu JQ. and Yamashita, U.
  • Organizer: International Cytokine Society Conference 2007
  • Place of Presentation: San Francisco, CA,
  • Year and Date: 2007-10-28
• [Presentation] Brain-derived neurotrophic factor (BDNF) produced by leukemia cell attenuated cytokine production in macrophage (2007)
  • Author(s): Yoshida, Y, et. al.
  • Organizer: International Cytokine Society Conference2007
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2007-10-28
• [Presentation] IL-1シグナルにおける分子標的薬 (2007)
  • Author(s): 吉田安宏, 山下優毅
  • Organizer: (Symposium session)第72回日本サイトカイン・インターフェロン学術集会
  • Place of Presentation: 京都
  • Year and Date: 2007-07-06
• [Presentation] IL-1シグナルにおける分子標的薬 (2007)
  • Author(s): 吉田 安宏, 他
  • Organizer: 第72回日本サイトカイン・インターフェロン学術集会
  • Place of Presentation: 京都
  • Year and Date: 2007-07-06
• [Book] 炎症と免疫における分子標的治療の新展開IL-1 (2007)
  • Author(s): 吉田安宏, 山下優毅
  • Publisher: 先端医学社