Analysis for the effect of silica particle exposure on immune system

• Project/Area Number: 25460825
• 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: Kawasaki Medical School
• Principal Investigator: Lee Suni 川崎医科大学, 医学部, 助教 (70414026)
• Co-Investigator(Kenkyū-buntansha): Otsuki Takemi 川崎医科大学, 医学部, 教授 (40160551) ; Nishimura Yasumitsu 川崎医科大学, 医学部, 准教授 (90360271)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 粉塵曝露 / 珪酸 / 自己免疫疾患 / 免疫動態

Outline of Final Research Achievements

Silicosis patients frequently complicate with autoimmune diseases. Here, we analyzed the effect of silica particles on peripheral blood mononuclear cells (PBMC) in vitro and plasma factors to compare between silicosis patients (Sil) and healthy volunteers (HV). We found IL-6 and IL-23 were increased in culture media after silica particle exposure on PBMC from HV. Both cytokines are essential for polarization and maintain to Th17, critical T cell subset for autoimmune pathogenesis. Dysregulation of apoptosis has been considered to play a role in the pathogenesis of autoimmune diseases. DcR3 is known as an intrinsic decoy receptor inhibits FasL-induced apoptosis. Although plasma DcR3 and several major autoantibodies were increased in Sil, there are no correlation between DcR3 and the other clinical factors including autoantibodies.
Taken together, silica particles affect directly on PBMC to induce Th17 subset. Plasma DcR3 elevation in Sil indicates abnormal activation of immune system.

Research Products

• [Journal Article] ヒトT細胞株への白石綿・青石綿継続曝露に伴う細胞特性の変化． (2016)
  • Author(s): 李順姫，前田恵，松﨑秀紀，武井直子，山本祥子，幡山圭代，吉留 敬，西村泰光，大槻剛巳．
  • Journal Title: 日本予防医学雑誌 Volume: 10 Pages: 119-125
  • NAID: 40020930413
  • Peer Reviewed
• [Journal Article] Targeting LDH enzymes with a stiripentol analog to treat epilepsy. (2015)
  • Author(s): Sada N, Lee S, Katsu T, Otsuki T, Inoue T
  • Journal Title: Science Volume: 347 Issue: 6228 Pages: 1362-1367
  • DOI: 10.1126/science.aaa1299
  • Peer Reviewed / Acknowledgement Compliant
• [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] 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] 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] 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
• [Journal Article] Exploration of biomarkers for asbestos exposure and occurrence of malignant mesothelioma based on the immunological effects of asbestos (2013)
  • Author(s): Matsuzaki H, Lee S, Kumagai-Takei N, Hayashi H, Miura Y, Chen Y, Maeda M, Yamamoto S, Hatayama T, Nishimura Y, Otsuki T
  • Journal Title: J Postgenomics: Drug & Biomarker Dev Volume: S2 Issue: 02 Pages: 1-6
  • DOI: 10.4172/2153-0602.s2-001
  • Peer Reviewed
• [Presentation] Study for Immunological Importance of Increased Plasma Decoy Receptor 3 Level in Silicosis (2016)
  • Author(s): Lee S. Nishimura Y, Yamamoto S, Hatayama T, Matsuzaki H, Kumagai-Takei N, Yoshitome K, Hayashi H, Uragami K, Kusaka M, Fujimoto W, Otsuki T.
  • Organizer: The 55th Annual Meeting of the Society of Toxicology
  • Place of Presentation: New Orleans, Louisiana, U.S.A．
  • Year and Date: 2016-03-13
  • Int'l Joint Research
• [Presentation] 珪肺症における血清DcR3分子の病態における位置付け (2015)
  • Author(s): 李順姫，大槻剛巳，松崎秀紀，武井直子，吉留敬，西村泰光，草加勝康，浦上更三
  • Organizer: 第59回中国四国合同産業衛生学会
  • Place of Presentation: 愛媛大学城北キャンパス南加記念ホール（松山）
  • Year and Date: 2015-12-05
• [Presentation] 珪肺症における免疫異常：血漿 Decoy Receptor 3 の位置付け診断指標の構築 (2015)
  • Author(s): 大槻剛巳，李順姫，武井直子，松崎秀紀，吉留敬，西村泰光，林宏明，浦上更三，草加勝康，藤本亘
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: ANAクラウンプラザホテル金沢など（金沢）
  • Year and Date: 2015-10-16
• [Presentation] 自己免疫疾患未発症珪肺症例における血漿免疫グロブリンとBAFF値の解析 (2015)
  • Author(s): 李順姫，西村泰光，山本祥子，幡山圭代，松崎秀紀，武井直子，吉留敬，大槻剛巳．
  • Organizer: 第22回日本免疫毒性学会学術年会
  • Place of Presentation: 京都大学百周年時計台記念館国際交流ホール（京都）
  • Year and Date: 2015-09-10
• [Presentation] 珪肺症患者由来血漿における自己抗体および液性因子の解析 (2015)
  • Author(s): 李順姫
  • Organizer: 第6回川崎医科大学学術集会
  • Place of Presentation: 川崎医科大学M-800教室・7/8F学生教員ラウンジ（倉敷）
  • Year and Date: 2015-08-01
• [Presentation] Analysis between blood DcR3 level, autoantibodies and respiratory score in silicosis patients. (2015)
  • Author(s): Lee S, Nishimura Y, Yamamoto S, Hatayama T, Matsuzaki H, Kumagai-Takei N, Yoshitome K, Otsuki T.
  • Organizer: 31st ICOH (International Congress on Occupational Health)
  • Place of Presentation: COEX Convention Center, Seoul, Korea
  • Year and Date: 2015-05-31
  • Int'l Joint Research
• [Presentation] Differences of immunological effects of crystalline silica and asbestos fibers on regulatory T cell (2015)
  • Author(s): Lee S, Otsuki T.
  • Organizer: The 54th Annual Meeting of the Society of Toxicology
  • Place of Presentation: San Diego Convention Center in San Diego, California, 米国
  • Year and Date: 2015-03-24
  • Invited
• [Presentation] Plasma DcR3 which inhibits Fas-induced apoptosis is increased in silicosis patients who are non-onset autoimmune diseases. (2014)
  • Author(s): Lee S, Nishimura Y, Matsuzaki H, Kumagai-Takei N, Ostuki T.
  • Organizer: The 43rd Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: 京都国際会館、京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] 自己免疫疾患未発症珪肺症例にいおける血中DcR3値と他の自己抗体値や呼吸機能検査値との関連 (2014)
  • Author(s): 李順姫，西村泰光，山本祥子，幡山圭代，松﨑秀紀，武井直子，吉留敬，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・国際会議場、徳島
  • Year and Date: 2014-09-11 – 2014-09-12
• [Presentation] Analysis of blood DcR3 concentration and its correlation to autoantibodies in silicosis patients. (2014)
  • Author(s): Lee S, Nishimura Y, Yamamoto S, Hatayama T, Matsuzaki H, Kumagai-Takei N, Yoshitome K, Otsuki T.
  • Organizer: The 21st The Asian Association for Occupational Health
  • Place of Presentation: Hilton Fukuoka Sea Halk、福岡
  • Year and Date: 2014-09-02 – 2014-09-04
• [Presentation] 珪肺症例における血漿中DcR3値と各種自己免疫疾患関連因子との相関性の検討 (2014)
  • Author(s): 李順姫，西村泰光，松崎秀紀，武井直子，山本祥子，幡山圭代，大槻剛巳.
  • Organizer: 第84回日本衛生学会学術総会
  • Place of Presentation: 岡山コンベンションセンター、岡山
  • Year and Date: 2014-05-25 – 2014-05-27
• [Presentation] 石綿の低濃度長期曝露がTreg様モデル細胞株 MT-2細胞の細胞増殖に及ぼす影響 (2014)
  • Author(s): 李順姫，松崎秀紀，前田恵，武井直子，西村泰光，大槻剛巳.
  • Organizer: 第87回日本産業衛生学会
  • Place of Presentation: 岡山コンベンションセンター（岡山）
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] Analysis of blood DcR3 concentration andits correlation to clinical paramaters of autoimmune diseases in silicosis patients. (2014)
  • Author(s): Lee S, Nishimra Y, Yamamoto S, Hatayama T, Mastuzaki H, Kumagai-Takei N, Hayashi H, Kusaka M, Fujimoto W, Otsuki T.
  • Organizer: The 53rd annual Meeting. Society of Toxicology
  • Place of Presentation: Phoenix, AZ, USA
• [Presentation] 珪肺症例における血漿DcR3値と各種自己免疫疾患関連因子との相関性の検討 (2014)
  • Author(s): 李 順姫，西村泰光，山本祥子，幡山圭代，松崎秀紀，武井直子，大槻剛巳.
  • Organizer: 第13回分子予防環境医学研究会
  • Place of Presentation: 和歌山県民文化会館 大会議室
• [Presentation] Continuous exposure of asbestos on Treg model cell line MT-2 affects cellcycle progression and cell surbvival. (2013)
  • Author(s): Lee S, Matsuzaki H, Maeda M, Kumagai-Takei N, Nishimura , Otsuki T.
  • Organizer: 2013日本免疫学会・学術集会
  • Place of Presentation: 千葉、幕張メッセ
• [Presentation] Long-term exposure of asbestos affects cell cycle and cell death in Treg model cell line MT-2. (2013)
  • Author(s): Lee S, Matsuzaki H, Maeda M, Kumagai-Takei N, Nishimura Y, Otsuki T.
  • Organizer: 6th International Symposium on Nanotechnology, Occupational and Environmental Health.
  • Place of Presentation: Nagoya Congress Center
• [Presentation] 石綿長期曝露制御性T細胞株における細胞周期制御因子の発現動態の解析 (2013)
  • Author(s): 李順姫，松﨑秀紀，武井直子，西村泰光，大槻剛巳．
  • Organizer: 第20回石綿・中皮腫研究会
  • Place of Presentation: 東京、(公財)がん研究会がん研究所 吉田講堂
• [Book] Immunostimulation (2014)
  • Author(s): Lee S, Maeda M, Hayashi H, Matsuzaki H, Kumagai-Takei N, Nishimura Y, Otsuki T.
  • Total Pages: 18
  • Publisher: InTech publisher