Effect of asbestos on apoptosis, proliferation and cytokine production of regulatory T cells

• Project/Area Number: 25860471
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hygiene and public health
• Research Institution: Kawasaki Medical School
• Principal Investigator: MATSUZAKI Hidenori 川崎医科大学, 医学部, 助教 (80335463)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: アスベスト / 腫瘍免疫 / 制御性T細胞 / アポトーシス / 転写因子 / FoxP3 / GATA1

Outline of Final Research Achievements

We studied effect of long-term exposure to asbestos with MT-2 cells as a regulatory T cell model. It was revealed that long-term exposure to asbestos reduced transcription factors, FoxO1 and FoxP3, in MT-2 cells. Furthermore, FoxO1 target molecules were suppressed by long-term exposure to asbestos. Expression of recombinant FoxP3 enhanced sensitivity to asbestos. These results suggest that exposure to asbestos modifies regulatory T cell function through the inactivation of FoxO1 and FoxP3. These are important to elucidate effect of asbestos on regulatory T cells and tumor immunity.

Research Products

• [Journal Article] Functional properties of CD8+ lymphocytes in patients with pleural plaque and malignant mesothelioma (2014)
  • Author(s): Kumagai-Takei N, Nishimura Y, Maeda M, Hayashi H, Matsuzaki H, Lee S, Kishimoto T, Fukuoka K, Nakano T, and Otsuki T
  • Journal Title: J Immunol Res Volume: 2014 Pages: 10-20
  • DOI: 10.1155/2014/670140
  • Peer Reviewed / Open Access
• [Journal Article] Chronic exposure to asbestos enhances TGF-β1 production in the human adult T cell leukemia virus-immortalized T cell line MT-2. (2014)
  • Author(s): Maeda M, Chen Y, Hayashi H, Kumagai-Takei N, Matsuzaki H, Lee S, Nishimura Y, Otsuki T.
  • Journal Title: Int J Oncol. Volume: 45 Issue: 6 Pages: 2522-2532
  • DOI: 10.3892/ijo.2014.2682
  • Peer Reviewed / Open Access
• [Journal Article] Silica exposure and altered regulation of autoimmunity (2014)
  • Author(s): Lee S, Matsuzaki H, Kumagai-Takei N, Yoshitome K, Maeda M, Chen Y, Kusaka M, Urakami K, Hayashi H, Fujimoto W, Nishimura Y, Otsuki T,
  • Journal Title: Environ Health Prev Med Volume: 19 Issue: 5 Pages: 322-9
  • DOI: 10.1007/s12199-014-0403-9
  • NAID: 50009312838
  • Peer Reviewed / Open Access
• [Journal Article] Alteration of cytoskeletal molecules in a human T cell line caused by continuous exposure to chrysotile asbestos. (2013)
  • Author(s): Maeda, M., Chen, Y., Kumagai-Takei, N., Hayashi, H., Matsuzaki, H., Lee, S., Hiratsuka, JI., Nishimura, Y., Kimura, Y., Otsuki T.
  • Journal Title: Immunobiology Volume: (in press) Issue: 9 Pages: 1184-91
  • DOI: 10.1016/j.imbio.2013.04.007
  • Peer Reviewed
• [Journal Article] Altered functions of alveolar macrophages and NK cells involved in asbestos-related diseases. (2013)
  • Author(s): Nishimura, Y., Maeda, M.,Kumagai-Takei, N., Lee, S., Matsuzaki, H., Wada, Y., Nishiike-Wada, T., Iguchi, H., Otsuki, T.
  • Journal Title: Environ. Health Prev. Med. Volume: 18(3) Issue: 3 Pages: 198-204
  • DOI: 10.1007/s12199-013-0333-y
  • NAID: 10031175980
  • Peer Reviewed
• [Journal Article] Effect of asbestos exposure on differentiation of cytotoxic T lymphocytes in MLR of human PBMCs (2013)
  • Author(s): Kumagai-takei N, Nishimura Y, Maeda M, Hayashi H, Matsuzaki H, Lee S, Hiratsuka J, Otsuki T
  • Journal Title: Am J Respir Cell Mol Biol Volume: 49(1) Issue: 1 Pages: 28-36
  • DOI: 10.1165/rcmb.2012-0134oc
  • Peer Reviewed
• [Presentation] 転写因子FoxP3とGATA1に対するアスベスト長期曝露の影響 (2015)
  • Author(s): 松崎秀紀，李順姫，前田恵，武井直子，西村泰光，大槻剛巳
  • Organizer: 第85回日本衛生学会学術総会
  • Place of Presentation: 和歌山県民文化会館（和歌山県・和歌山市）
  • Year and Date: 2015-03-27
• [Presentation] 制御性T細胞の調節因子に対するアスベスト長期曝露の影響 (2015)
  • Author(s): 松崎秀紀、李順姫、前田恵、武井直子、吉留敬、西村泰光、大槻剛巳
  • Organizer: 第14回分子予防環境医学研究会
  • Place of Presentation: 大阪市立大学医学部（大阪府・大阪市）
  • Year and Date: 2015-02-14
• [Presentation] MT-2細胞に対するアスベト長期曝露の影響 (2014)
  • Author(s): 松﨑秀紀，李順姫，前田恵，武井直子，西村泰光，大槻剛巳
  • Organizer: 第21回石綿・中皮腫研究会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2014-10-11
• [Presentation] ヒトT細胞株MT-2細胞に対するアスベスト長期曝露の影響 (2014)
  • Author(s): 松﨑秀紀，李順姫，前田恵，武井直子，西村泰光，大槻剛巳
  • Organizer: 第21回日本免疫毒性学会学術年会
  • Place of Presentation: 徳島文理大学（徳島県・徳島市）
  • Year and Date: 2014-09-11
• [Presentation] Molecular mechanisms of asbestos-induced apoptosis in MT-2 cells. (2014)
  • Author(s): Matsuzaki H, Lee S, Maeda M, Kumagai-Takei N, Nishimura Y. Otsuki T.
  • Organizer: The 21st The Asian Association for Occupational Health
  • Place of Presentation: ヒルトン福岡シーホーク（福岡県・福岡市）
  • Year and Date: 2014-09-02
• [Presentation] FoxO1 Regulates Apoptosis Induced by Asbestos in the Human T Cell Line MT-2 (2014)
  • Author(s): Hidenori Matsuzaki, Suni Lee, Megumi Maeda, Naoko Kumagai-Takei, Yasumitsu Nishimura, and Takemi Otsuki
  • Organizer: 53rd Annual Meeting of the Society of Toxicology
  • Place of Presentation: フェニックスコンベンションセンター（アメリカ）
• [Presentation] Molecular basis of asbestos-induced apoptosis in MT-2 cells (2013)
  • Author(s): Hidenori Matsuzaki, Suni Lee, Megumi Maeda, Naoko Kumagai-Takei, Yasumitsu Nishimura, and Takemi Otsuki
  • Organizer: 第42会日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] アスベスト長期曝露により発現の低下するFoxO1の役割 (2013)
  • Author(s): 松﨑 秀紀、李 順姫、前田 恵、武井 直子、西村 泰光、大槻 剛巳
  • Organizer: 第２０回日本免疫毒性学会学術集会
  • Place of Presentation: 東海大学代々木キャンパス（東京）
• [Presentation] Down-regulation of FoxO1 in MT-2 cells induced by long-term exposure to asbestos (2013)
  • Author(s): Hidenori Matsuzaki, Suni Lee, Megumi Maeda, Naoko Kumagai-Takei, Yasumitsu Nishimura, and Takemi Otsuki
  • Organizer: The 6th International Symposium on Nanotechnology, Occupational and Environmental Health.
  • Place of Presentation: 名古屋国際会議場（愛知）