Effect of short-term and long-term exposure of asbestos on regulatory T cells

• Project/Area Number: 15K08788
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hygiene and public health
• Research Institution: Prefectural University of Hiroshima (2017); Kawasaki Medical School (2015-2016)
• Principal Investigator: Matsuzaki Hidenori 県立広島大学, 生命環境学部, 助教 (80335463)
• Co-Investigator(Kenkyū-buntansha): 大槻 剛巳 川崎医科大学, 医学部, 教授 (40160551) ; 李 順姫 川崎医科大学, 医学部, 助教 (70414026)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: アスベスト / 腫瘍免疫 / アポトーシス / FoxP3 / DNAメチル化 / ミトコンドリア / DNA損傷 / 悪性中皮腫 / 制御性T細胞

Outline of Final Research Achievements

Asbestos is known to cause lung cancer and malignant mesothelioma. We are proposing that asbestos inhibit tumor immune responses. In this study, we studied effect of exposure of asbestos on MT-2 as a regulatory T cell model. It was revealed that short-term exposure with high-dose asbestos induces mitochondrial dysfunction and DNA damage, and that long-term exposure of low-dose asbestos reduces transcription factor FoxP3 expression through the mechanisms independent of upstream transcription factors and DNA methylation.

Research Products

• [Journal Article] Induction of IL-17 production from human peripheral blood CD4+ cells by asbestos exposure (2017)
  • Author(s): Maeda Megumi、Chen Ying、Lee Suni、Kumagai-Takei Naoko、Yoshitome Kei、Matsuzaki Hidenori、Yamamoto Shoko、Hatayama Tamayo、Ikeda Miho、Nishimura Yasumitsu、Otsuki Takemi
  • Journal Title: International Journal of Oncology Volume: 50 Issue: 6 Pages: 2024-2032
  • DOI: 10.3892/ijo.2017.3991
  • NAID: 120006363419
  • Peer Reviewed
• [Journal Article] Clinical evaluation of CENP-B and Scl-70 autoantibodies in silicosis patients. (2017)
  • Author(s): Lee, S., Hayashi, H., Kumagai-Takei, N., Matsuzaki, H., Yoshitome, K., Nishimura, Y., Uragami, K., Kusaka, M., Yamamoto, S., Ikeda, M., Hatayama, T., Fujimoto, W., Otsuki, T.
  • Journal Title: Exp. Ther. Med. Volume: 13 Issue: 6 Pages: 2616-2622
  • DOI: 10.3892/etm.2017.4331
  • Peer Reviewed
• [Journal Article] Search for biomarkers of asbestos exposure and asbestos-induced cancers in investigations of the immunological effects of asbestos (2017)
  • Author(s): Matsuzaki Hidenori、Kumagai-Takei Naoko、Lee Suni、Maeda Megumi、Sada Nagisa、Hatayama Tamayo、Yamamoto Shoko、Ikeda Miho、Yoshitome Kei、Min Yu、Nishimura Yasumitsu、Otsuki Takemi
  • Journal Title: Environmental Health and Preventive Medicine Volume: 22 Issue: 1
  • DOI: 10.1186/s12199-017-0661-4
  • NAID: 210000130229
  • Peer Reviewed / Open Access
• [Journal Article] The Suppressed Induction of Human Mature Cytotoxic T Lymphocytes Caused by Asbestos Is Not due to Interleukin-2 Insufficiency (2016)
  • Author(s): Kumagai-Takei, N. Nishimura, Y. Matsuzaki, H. Lee, S. Yoshitome, K. Hayashi, H. Otsuki, T.
  • Journal Title: J Immunol Res Volume: 2016 Pages: 1-10
  • DOI: 10.1155/2016/7484872
  • Peer Reviewed / Open Access
• [Journal Article] Biological effects of Cloth containing specific ore powder in patients with pollen allergy. (2016)
  • Author(s): Lee, S., Okamoto, H., Yamamoto, S., Hatayama, T., Matsuzaki, H., Kumagai-Takei, N., Yoshitome, K., Nishimura, Y., Sato, T., Kirita, Y., Fujii, Y., Otsuki, T.
  • Journal Title: Biomed. Environmental Sci. Volume: 29 Pages: 77-84
  • Peer Reviewed
• [Journal Article] Silica and mineral silicates causing autoimmune diseases. (2016)
  • Author(s): Lee, S., Matsuzaki, H., Kumagai-Takei, N., Yamamoto, S., Hatayama, T., Yoshitome, K., Nishimura, Y., Otsuki, T.
  • Journal Title: Kawasaki Med. J. Volume: 42 Pages: 15-24
  • NAID: 110010041934
  • Peer Reviewed
• [Journal Article] FoxO1 Regulates Apoptosis Induced by Asbestos in the MT-2 Human T-Cell Line. (2016)
  • Author(s): Matsuzaki, H., Lee, S., Maeda, M., Kumagai-Takei, N., Nishimura, Y., Otsuki, T.
  • Journal Title: Immunotoxicol. Volume: 13 Pages: 1-8
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Environmental factors and human health: fibrous and particulate substance-induced immunological disorders and construction of a health-promoting living environment (2016)
  • Author(s): Otsuki, T. Matsuzaki, H. Lee, S. Kumagai-Takei, N. Yamamoto, S. Hatayama, T. Yoshitome, K. Nishimura, Y.
  • Journal Title: Environ Health Prev Med Volume: 21 Issue: 2 Pages: 71-81
  • DOI: 10.1007/s12199-015-0499-6
  • NAID: 210000000423
  • Peer Reviewed / Open Access
• [Journal Article] The proliferative effects of asbestos-exposed peripheral blood mononuclear cells on mesothelial cells (2016)
  • Author(s): Maki Y, Nishimura Y, Toyooka S, Soh J, Tsukuda K, Shien K, Furukawa M, Muraoka T, Ueno T, Tanaka N, Yamamoto H, Asano H, Maeda M, Kumagai-Takei N, Lee S, Matsuzaki H, Otsuki T, Miyoshi S
  • Journal Title: Oncology Letters Volume: 11 Issue: 5 Pages: 3308-3316
  • DOI: 10.3892/ol.2016.4412
  • Peer Reviewed / Open Access
• [Journal Article] Enhancement of regulatory T cell-like suppressive function in MT-2 by long-term and low-dose exposure to asbestos. (2015)
  • Author(s): Ying, C., Maeda, M., Nishimura, Y., Kumagai-Takei, N., Hayashi, H., Matsuzaki, H., Lee, S., Yoshitome, K., Yamamoto, S., Hatayama, T., Otsuki, T.
  • Journal Title: Toxicology Volume: 338 Pages: 86-94
  • DOI: 10.1016/j.tox.2015.10.005
  • Peer Reviewed
• [Journal Article] Investigating methods regarding diagnostic and prognostic biomarkers for malignant mesothelioma. (2015)
  • Author(s): Matsuzaki, H., Lee, S., Kumagai-Takei, N., Yoshitome, K., Yamamoto S, Hatayama T, Nishimura, Y., Otsuki, T.
  • Journal Title: Kawasaki Med. J. Volume: 41 Pages: 13-22
  • NAID: 110009926233
  • Peer Reviewed
• [Journal Article] Enhancement of NK Cell Cytotoxicity Induced by Long-Term Living in Negatively Charged-Particle Dominant Indoor Air-Conditions. (2015)
  • Author(s): Nishimura, Y., Takahashi, K., Mase, A., Kotani, M., Ami, K., Maeda, M., Shirahama, T., Lee, S., Matsuzaki, H., Kumagai-Takei, N., Yoshitome, K., Otsuki, T.
  • Journal Title: PlosOne Volume: 10 Issue: 7 Pages: e0132373-e0132373
  • DOI: 10.1371/journal.pone.0132373
  • Peer Reviewed / Open Access
• [Journal Article] Exposure to negaively-charged particle domitant air-conditions on human lymphocytes in vitro activates immunological responses. (2015)
  • Author(s): Nishimura, Y., Takahashi, K., Masae, A., Kotani, M., Ami, K., Maeda, M., Shirahama, T., Lee, S., Matsuzaki, H., Kumagai-Takei, N., Yoshitome, K., Otsuki, T.
  • Journal Title: Immunobiology Volume: 220 Issue: 12 Pages: 1359-1368
  • DOI: 10.1016/j.imbio.2015.07.006
  • Peer Reviewed
• [Journal Article] Functional alteration of natural killer cells and cytotoxic T lymphocytes upon asbestos exposure and in malignant mesothelioma patients. (2015)
  • Author(s): Nishimura, Y., Kumagai-Takei, N., Matsuzaki, H., Lee, S., Maeda, M., Kishimoto, T., Fukuoka, K., Nakano, T., Otsuki, T.
  • Journal Title: Biomed. Res. Int. Volume: 2015 Pages: 1-9
  • DOI: 10.1155/2015/238431
  • Peer Reviewed / Open Access
• [Presentation] MT-2細胞に対する短期および長期のアスベスト曝露の影響の研究 (2017)
  • Author(s): 松﨑秀紀，李順姫，前田恵，武井直子，西村泰光，吉留敬，大槻剛巳
  • Organizer: 第87回日本衛生学会学術総会
  • Place of Presentation: フェニックス・シーガイア・リゾート（宮崎県宮崎市）
  • Year and Date: 2017-03-26
• [Presentation] Effect of Short-Term and Long-Term Exposure of Asbestos on Human T Cell Line MT-2. (2017)
  • Author(s): Matsuzaki, H., Lee, S., Maeda, M., Kumagai-Takei, N., Yoshitome, K., Nishimura, Y., Otsuki, T.
  • Organizer: The 56th Annual Meeting of the Society of Toxicology
  • Place of Presentation: The Baltimore Convention Center (Baltimore, Maryland, USA)
  • Year and Date: 2017-03-12
  • Int'l Joint Research
• [Presentation] アスベスト曝露により誘導されるストレス応答の研究 (2017)
  • Author(s): 松﨑秀紀、李順姫、前田 恵、武井直子、吉留 敬、西村泰光、大槻剛巳
  • Organizer: 第24回日本免疫毒性学会学術年会
• [Presentation] MT-2 細胞を用いた短期および長期のアスベスト曝露の影響の解析 (2016)
  • 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23回日本免疫毒性学会学術年会
  • Place of Presentation: 北九州国際会議場（福岡県北九州市)
  • Year and Date: 2016-09-05
• [Presentation] The Role of Transcription Factor FoxP3 in the Asbestos-Induced Apoptosis in MT-2 Cells. (2016)
  • Author(s): Matsuzaki H. Lee S, Maeda M, Kumagai-Takei N, Yoshitome K, Nishimura Y, Otsuki T.
  • Organizer: The 55th Annual Meeting of the Society of Toxicology
  • Place of Presentation: Ernest N. Morial Convention Center, New Orleans, USA
  • Year and Date: 2016-03-14
  • Int'l Joint Research
• [Presentation] FoxP3 に対するアスベスト長期曝露影響の解析 (2015)
  • 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22回日本免疫毒性学会学術年会
  • Place of Presentation: 京都大学（京都）
  • Year and Date: 2015-09-11
• [Presentation] Role of FoxO1 and FoxP3 in Asbestos-induced Apoptosis of MT-2 Cells. (2015)
  • Author(s): Matsuzaki H, Lee S, Maeda M, Kumagai-Takei N, Nishimura Y, Otsuki T.
  • Organizer: 31st International Congress on Occupational Health
  • Place of Presentation: COEX Convention Center, Seoul, Korea
  • Year and Date: 2015-06-01
  • Int'l Joint Research
• [Presentation] Matsuzaki H, Lee S, Maeda M, Kumagai-Takei N, Nishimura Y, Otsuki T. (2015)
  • Author(s): The altelation of FoxP3 and GATA-1 in asbestos-treated human T cell line MT-2.
  • Organizer: 31st International Congress on Occupational Health
  • Place of Presentation: COEX Convention Center, Seoul, Korea
  • Year and Date: 2015-05-31
  • Int'l Joint Research