BDNF produced by leukemia cells induced regulatory T cells

• Project/Area Number: 21591253
• 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 産業医科大学, 医学部, 准教授 (10309958)
• Co-Investigator(Kenkyū-buntansha): TSUKADA Junichi 産業医科大学, 大学病院, 准教授 (20227367)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 白血病 / BDNF / Treg(制御性T細胞) / TrkB / RhoA / NFAT

Research Abstract

We found that BDNF is continuously secreted by leukemia cells. BDNF induced regulatory T cells, which function as a suppressor cells to immune systems. It might help for tumor progression. In addition, we observed that some serum from a patient of adult T cell leukemia contain high amount of BDNF than healthy donor. It is thought that BDNF is very interesting molecules for modulating an antitumor effect.

Research Products

• [Journal Article] Differential mRNA express ion of neuroimmune markers in the hippocampus of infant mice following toluene exposure during brain developmental period (2012)
  • Author(s): Tin-Tin-Win-Shwe, Kunugita, N., Yoshida, Y., Nakajima, D., Tsukahara, S., Arashidani, K. and Fujimaki, H.
  • Journal Title: Journal of Applied Toxicology Volume: 32 Issue: 2 Pages: 126-134
  • DOI: 10.1002/jat.1643
  • Peer Reviewed
• [Journal Article] Apoptosis induction through proteasome inhibitory activity of cucurbitacin D in human T-cell leukemia (2011)
  • Author(s): Ding, N., Yamashita, U., Matsuoka, H., Sugiura, T., Tsukada, J., Noguchi, J. and Yoshida, Y.
  • Journal Title: Cancer Volume: 117 Issue: 12 Pages: 2735-46
  • DOI: 10.1002/cncr.25711
  • Peer Reviewed
• [Journal Article] The CCAAT/enhancer(C/EBP) family of basic-leucine zipper(bZIP) transcription factors is a multifaceted highly-regulated system for gene regulation (2011)
  • Author(s): Tsukada, J., Yoshida, Y., Kominato, Y. and Auron, P. E.
  • Journal Title: Cytokine Volume: 54 Pages: 6-19
  • Peer Reviewed
• [Journal Article] Role of hippocampal TLR4 in neurotoxicity in mice following toluene exposure (2011)
  • Author(s): Tin-Tin-Win-Shwe, Yoshida, Y., Kunugita, N. and Fujimaki, H.
  • Journal Title: Neurotoxicology and Teratology Volume: 33 Pages: 598-602
  • Peer Reviewed
• [Journal Article] The CCAAT/enhancer (C/EBP) family of basic-leucine zipper (bZIP) transcription factors is a multifaceted highly-regulated system for gene regulation (2011)
  • Author(s): Tsukada, J., Yoshida Y., et al
  • Journal Title: Cytokine Volume: 54 Pages: 6-19
  • Peer Reviewed
• [Journal Article] Thymocytes are activated by toluene inhalation through the transcription factors NF-K B, STAT5 and NF-AT (2010)
  • Author(s): Liu, JQ., Yoshida, Y., Kunugita, N., Noguchi, J., Sugiura, T., Ding, N., Arashidani, K., Fujimaki, H. and Yamashita, U.
  • Journal Title: Journal of Applied Toxicology Volume: 30 Issue: 7 Pages: 656-660
  • DOI: 10.1002/jat.1536
  • Peer Reviewed
• [Journal Article] Does early life toluene exposure alter the expression of NMDA receptor subunits and signal transduction pathway in infant mouse hippocampus (2010)
  • Author(s): Tin-Tin-Win-Shwe, Yoshida, Y., Kunugita, N., Tsukahara, S. and Fujimaki, H.
  • Journal Title: Neuro Toxi Volume: 31 Pages: 647-653
  • Peer Reviewed
• [Journal Article] Enhanced effect of new proteasome inhibitor cucurbitacin D on LPS-induced IL-1 production in Raw264 cells (2010)
  • Author(s): Yoshida, Y., Ding, N.
  • Journal Title: Proceedings of the Cytokines Pages: 39-43
  • Peer Reviewed
• [Journal Article] Thymocytes are activated by toluene inhalation through the transcription factors NF- κ, B, STAT5 and NF-AT. (2010)
  • Author(s): Liu, JQ., Yoshida Y., et al.
  • Journal Title: Journal of Applied Toxicology Volume: 30 Pages: 656-660
  • Peer Reviewed
• [Journal Article] Does early life toluene exposure alter the expression of NMDA receptor subunits and signal transduction pathway in infant mouse hippocampus? (2010)
  • Author(s): Tin-Tin-Win-Shwe, Yoshida Y., et al.
  • Journal Title: Neuro Toxicology Volume: 31 Pages: 647-653
  • Peer Reviewed
• [Journal Article] Formaldehyde inhalation activates signal transducer and activator of transcription 5 in immune cells. (2009)
  • Author(s): Yoshida, Y., Ding, N., Liu, JQ., Noguchi, J., Sugiura, T., Kunugita, N.
  • Journal Title: European Immunology Conference 39
  • Peer Reviewed
• [Presentation] Glucocorticoid receptor signaling is important for BDNF-induced CD4+Foxp3+and CD8+Foxp3+T cells (2011)
  • Author(s): 吉田安宏
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2011-11-28
• [Presentation] Glucocorticoid receptor signaling is important for BDNF-induced CD4+ Foxp3+ and CD8+ Foxp3+ T cells (2011)
  • Author(s): 吉田安宏
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2011-11-28
• [Presentation] BDNF induces regulatory T cells (2011)
  • Author(s): 吉田安宏
  • Organizer: 第23回日本神経免疫学会学術集会
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2011-09-17
• [Presentation] Autocrine loop of BDNF is involved in cell growth of T cell leukemia cells (2011)
  • Author(s): 吉田安宏
  • Organizer: 金沢国際がん生物学シンポジウム
  • Place of Presentation: 金沢音楽堂(金沢)
  • Year and Date: 2011-05-26
• [Presentation] 神経栄養因子および抗アポトーシスタンパク質に対するフロン代替物質1-プロモプロパンの作用 (2010)
  • Author(s): 吉田安宏, ほか
  • Organizer: 平成22年度産業神経・行動学研究会「環境と脳のはたらき」
  • Place of Presentation: 北九州学研都市産学連携センター(北九州)
  • Year and Date: 2010-12-11
• [Presentation] 神経栄養因子および抗アポトーシスタンパク質に対するフロン代替物 質1-ブロモプロパンの作用 (2010)
  • Author(s): 吉田安宏, ほか
  • Organizer: 平成22年度産業神経・行動学研究会「環境と脳のはたらき」
  • Place of Presentation: 北九州(学術学研都市 会議室)
  • Year and Date: 2010-12-11
• [Presentation] Proteasome inhibitor cucurbitacin Dinduces autophagy in prostate cancer cells (2010)
  • Author(s): 宋媛, 丁守, 金沢保, 吉田安宏
  • Organizer: 第33回日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド(神戸)
  • Year and Date: 2010-12-10
• [Presentation] Proteasome inhibitor cucurbitacin D induces autophagy in prostate cancer cells (2010)
  • Author(s): 宋媛, 丁宇, 金沢保, 吉田安宏
  • Organizer: 第33回日本分子生物学会
  • Place of Presentation: 神戸(神戸国際会議場)
  • Year and Date: 2010-12-10
• [Presentation] Proteasome inhibitor, cucurbitacin D induces cell death in adult T-cell leukemia through apoptosis and autophagy (2010)
  • Author(s): 吉田安宏, 宋媛, 丁宇
  • Organizer: 第33回日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド(神戸)
  • Year and Date: 2010-12-09
• [Presentation] Proteasome inhibitor, cucurbitacin D induces cell death in adult T-cell leukemia through apoptosis and autophagy (2010)
  • Author(s): 吉田安宏, 宋媛, 丁宇
  • Organizer: 第33回日本分子生物学会
  • Place of Presentation: 神戸(神戸国際会議場)
  • Year and Date: 2010-12-09
• [Presentation] BDNF produced by leukemia cells attenuates cytokine production in macrophages and induced Foxp3 positive cells through NF-AT, Smad and RhoA (2010)
  • Author(s): Yoshida, Y. and Tsukada, J.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸ポートアイランド(神戸)
  • Year and Date: 2010-08-25
• [Presentation] Anti-proliferative activity of cucurbitacin D on T-cell leukemia through proteasome inhibition (2010)
  • Author(s): Ding, N. Yamashita, U. and Yoshida, Y.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸ポートアイランド(神戸)
  • Year and Date: 2010-08-25
• [Presentation] LPS induce Wnt5a via NF-κB and STAT1 signaling pathway (2010)
  • Author(s): Nanbara, H., Wara-aswapati, N., Yoshida, Y., et al
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸ポトアイラン(神戸)
  • Year and Date: 2010-08-25
• [Presentation] BDNF produced by leukemia cells attenuates cytokine production in macrophages and induced Foxp3 positive cells through NF-AT, Smad and RhoA. (2010)
  • Author(s): Yoshida, Y., Tsukada, J.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸(神戸国際会議場)
  • Year and Date: 2010-08-25
• [Presentation] Anti-proliferative activity of cucurbitacin D on Tcell leukemia through proteasome inhibition. (2010)
  • Author(s): Ding, N.Yamashita, U., Yoshida, Y.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸(神戸国際会議場)
  • Year and Date: 2010-08-25
• [Presentation] P.gingivalis LPS induce Wnt5a via NF-κBand STAT1 signaling pathway. (2010)
  • Author(s): Nanbara, H., Wara-aswapati, N., Yoshida, Y., et al.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸(神戸国際会議場)
  • Year and Date: 2010-08-25
• [Presentation] Analysis of mechanism of the I-1 indction by new prteasome inhibitor Cucurbitacin D (2010)
  • Author(s): Yoshida, Y.
  • Organizer: Bit's 3rd Annual World Cancer Congress 2010
  • Place of Presentation: シンガポールEXPO(シンガポール・シンガポール)
  • Year and Date: 2010-06-23
• [Presentation] Analysis of mechanism of the IL-1 induction by new proteasome inhibitor Cucurbitacin D (2010)
  • Author(s): Yoshida, Y.
  • Organizer: Bit's 3rd.Annual World Cancer Congress 2010
  • Place of Presentation: シンガポール(シンガポールEXPO)
  • Year and Date: 2010-06-23
• [Presentation] BDNF produced by leukemia cels modulates immune respones (2010)
  • Author(s): Yoshida, Y.
  • Organizer: 1st World Congress of Immunodiseases and Therapy
  • Place of Presentation: 北京国際コンベンションセンター(中国・北京)
  • Year and Date: 2010-05-16
• [Presentation] BDNF produced by leukemia cells modulates immune responses (2010)
  • Author(s): Yoshida, Y.
  • Organizer: 1st.World Congress of Immunodiseases and Therapy
  • Place of Presentation: 中国・北京(北京国際コンベンションセンター)
  • Year and Date: 2010-05-16
• [Presentation] Induction of apoptosis in T-cell leukemia by new drug which targeted a proteasome inhibition (2009)
  • Author(s): Yoshida, Y., Ding, N., Yamashita, U.
  • Organizer: World Congress of Gene-2009
  • Place of Presentation: Foshan Golden Sun Hotel(中国・佛山)
  • Year and Date: 2009-12-06
• [Presentation] Induction of apoptosis in T-cell leukemia by new drug which targeted aproteasome inhibition. (2009)
  • Author(s): Yoshida, Y., Ding, N., Yamashita, U.
  • Organizer: World Congress of Gene-2009
  • Place of Presentation: 中国・佛山(Foshan Golden Sun Hotel)
  • Year and Date: 2009-12-06
• [Presentation] BDNF produed by leukemia cell activatesAP1 and NF-AT, which resulted in induction of Foxp3 (2009)
  • Author(s): 吉田安宏, 丁寧, 山下優毅
  • Organizer: 第39回日本学会総会・学術集会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2009-12-03
• [Presentation] BDNF produced by leukemia cells activates AP1 and NF-AT, which resulted in induction of Foxp3. (2009)
  • Author(s): 吉田安宏, 丁〓, 山下優毅
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪(大阪国際会議場)
  • Year and Date: 2009-12-03
• [Presentation] Cucurbitacin Dの転写および転写後修飾によるIL-1β産生の調節機構 (2009)
  • Author(s): 丁寧, 吉田安宏, 山下優毅
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2009-12-02
• [Presentation] Cucurbitacin Dの転写および転写後修飾によるIL-1β産生の調節機構 (2009)
  • Author(s): Ding, N., 吉田安宏, 山下優毅
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪(大阪国際会議場)
  • Year and Date: 2009-12-02
• [Presentation] Triterpenoids cucurbitacin D isolated from cucurbitaceae induces apoptosis in adult T-cell leukemia through proteasome inhibtion (2009)
  • Author(s): Yoshida, Y., Ding, N., Yamashita, U.
  • Organizer: 2009 4th Medical Biotech Forum, International experts symposium
  • Place of Presentation: Dalian Municipal Party Committee Hotel(中国・大連)
  • Year and Date: 2009-08-08
• [Presentation] Triterpenoids cucurbitacin D isolated from cucurbitaceae induces apoptosis in adult T-cell leukemia through proteasome inhibition. (2009)
  • Author(s): Yoshida, Y., Ding, N., Yamashita, U.
  • Organizer: 2009 4th Medical Biotech Forum, International experts symposium
  • Place of Presentation: 中国・大連(Dalian Municipal Party Committee Hotel)
  • Year and Date: 2009-08-08