Molecular mechanisms of up-regulation of regulatory T cells induced by asbestos

• Project/Area Number: 23890237
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Hygiene
• Research Institution: Kawasaki Medical School
• Principal Investigator: MATSUZAKI Hidenori 川崎医科大学, 医学部, 助教 (80335463)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: アスベスト / がん / 腫瘍免疫 / 制御性 T 細胞 / アポトーシス / 悪性中皮腫 / 制御性T細胞 / 転写因子 / FOXO1 / 免疫

Research Abstract

We previously reported that MT-2 cells, model of regulatory T cells, showed resistance to high concentration of asbestos and up-regulation of IL-10 and TGFβ production after long-term exposure to low concentration of asbestos. In this study, we analyzed the involvement of transcription factors, FoxP3, NFAT and FoxO1, in change of functions of MT-2 cells induced by asbestos. It was revealed that long-term exposure to asbestos reduced expression of FoxP3 and FoxO1, and FoxO1 regulated apoptosis induced by asbestos. These results are important for elucidating the mechanism of up-regulation of regulatory T cell induced by asbestos.

Research Products

• [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] 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: (in press)
  • 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] Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite ona human T cell. (2012)
  • Author(s): Maeda, M., Yamamoto, S., Chen, Y.,Kumagai-Takei, N., Hayashi, H., Matsuzaki, H., Lee, S., Hatayama, T., Miyahara, N., Katoh, M., Hiratsuka, J., Nishimura, Y., Otsuki, T.
  • Journal Title: Sci. Total Environ. Volume: 429 Pages: 174-182
  • DOI: 10.1016/j.scitotenv.2012.04.043
  • Peer Reviewed
• [Journal Article] Asbestos-induced cellular and molecular alteration of immunocompetent cells and the relationship with chronic inflammation and carcinogenesis (2012)
  • Author(s): Matsuzaki Hidenori
  • Journal Title: Journal of Biomedicine and Biotechnology Volume: 2012 Pages: 1-9
  • DOI: 10.1155/2012/492608
  • Peer Reviewed
• [Journal Article] Environmental factors producing autoimmune dysregulation-Chronic activation of T cells caused by silica exposure (2012)
  • Author(s): Suni Lee
  • Journal Title: Immunobiology Volume: (Epub ahead of print) Issue: 7 Pages: 43-48
  • DOI: 10.1016/j.imbio.2011.12.009
  • Peer Reviewed
• [Journal Article] Functional and direct interaction between the RNA binding protein HuD and active Akt1 (2012)
  • Author(s): Toshinobu Fujiwara
  • Journal Title: Nucleic Acids Research Volume: 40(5) Issue: 5 Pages: 1944-1953
  • DOI: 10.1093/nar/gkr979
  • Peer Reviewed
• [Journal Article] Asbestos induces reduction of tumor immunity (2011)
  • Author(s): Kumagai-Takei Naoko
  • Journal Title: Clinical and Developmental Immunology Volume: 2011 Pages: 1-9
  • DOI: 10.1155/2011/481439
  • Peer Reviewed
• [Presentation] MT-2細胞のアポトーシス制御におけるFoxO1の役割 (2013)
  • Author(s): 松崎秀紀
  • Organizer: 第83回日本衛生学会学術総会
  • Place of Presentation: 金沢大学
• [Presentation] フォークヘッド転写因子FoxO1を介したMT-2細胞のアポトーシス調節機構の解析 (2013)
  • Author(s): 松崎秀紀
  • Organizer: 第12回分子予防環境医学研究会
  • Place of Presentation: つくばサイエンス・インフォメーションセンター
• [Presentation] フォークヘッド転写因子FoxO1を介したMT-2細胞のアポトーシス調節機構の解析 (2013)
  • Author(s): 松崎秀紀
  • Organizer: 第１２回分子予防環境医学研究会
  • Place of Presentation: つくばサイエンス・インフォメーションセンター （筑波）
• [Presentation] アスベスト長期曝露に起因する制御性T細胞モデル株MT-2における細胞増殖の変化 (2013)
  • Author(s): 李順姫
  • Organizer: 第１２回分子予防環境医学研究会
  • Place of Presentation: つくばサイエンス・インフォメーションセンター （筑波）
• [Presentation] CD8+リンパ球に注目した胸膜プラーク陽性者と悪性中皮腫患者の免疫学的特徴 (2013)
  • Author(s): 武井直子
  • Organizer: 第１２回分子予防環境医学研究会
  • Place of Presentation: つくばサイエンス・インフォメーションセンター （筑波）
• [Presentation] THE ROLE OF TRANSCRIPTION FACTOR FOXO1 IN ASBESTOS-INDUCED APOPTOSIS OF MT-2 CELLS (2013)
  • Author(s): Matsuzaki Hidenori
  • Organizer: 52nd Annual Meeting of the Society of Toxicology
  • Place of Presentation: Henry B. Gonzalez Convention Center（サンアントニオ、テキサス州、米国）
• [Presentation] LONG TERM EXPOSURE OF ASBESTOS ON MT-2 CELL AFFECTS CELL CYCLE PROGRESSION AND CELL DEATH (2013)
  • Author(s): Lee Suni
  • Organizer: 52nd Annual Meeting of the Society of Toxicology
  • Place of Presentation: Henry B. Gonzalez Convention Center（サンアントニオ、テキサス州、米国）
• [Presentation] DIFFERENCE IN FUNCTIONAL PROPERTY OF CD8+ LYMPHOCYTES BETWEEN PATIENTS WITH PLEURAL PLAQUE AND MALIGNANT MESOTHELIOMA (2013)
  • Author(s): Kumagai-Takei Naoko
  • Organizer: 52nd Annual Meeting of the Society of Toxicology
  • Place of Presentation: Henry B. Gonzalez Convention Center（サンアントニオ、テキサス州、米国）
• [Presentation] Effects of asbestos exposure on regulatory role of NK cells for expanded autologous CD4+ T cells (2013)
  • Author(s): Nishimura Yasumitsu
  • Organizer: 52nd Annual Meeting of the Society of Toxicology
  • Place of Presentation: Henry B. Gonzalez Convention Center（サンアントニオ、テキサス州、米国）
• [Presentation] RESISTANCE TO ASBESTOS-INDUCED APOPTOSIS WITH CONTINUOUS EXPOSURE TO CROCIDOLITE ON A HUMAN T CELL (2013)
  • Author(s): Otsuki Takemi
  • Organizer: 52nd Annual Meeting of the Society of Toxicology
  • Place of Presentation: Henry B. Gonzalez Convention Center（サンアントニオ、テキサス州、米国）
• [Presentation] MT-2細胞のアポトーシス制御におけるFoxO1の役割 (2013)
  • Author(s): 松崎秀紀
  • Organizer: 第８３回日本衛生学会学術総会
  • Place of Presentation: 金沢大学・金沢美術工芸大学（金沢）
• [Presentation] 石綿長期曝露Treg様モデル細胞株MT-2細胞における細胞増殖の変化 (2013)
  • Author(s): 李順姫
  • Organizer: 第８３回日本衛生学会学術総会
  • Place of Presentation: 金沢大学・金沢美術工芸大学（金沢）
• [Presentation] 石綿曝露によるCD8+T細胞のCTL分化抑制におけるIL-2関与の検討 (2013)
  • Author(s): 武井直子
  • Organizer: 第８３回日本衛生学会学術総会
  • Place of Presentation: 金沢大学・金沢美術工芸大学（金沢）
• [Presentation] 悪性中皮腫および全身性強皮症患者における免疫関連遺伝子発現動態の解析 (2013)
  • Author(s): 西村泰光
  • Organizer: 第８３回日本衛生学会学術総会
  • Place of Presentation: 金沢大学・金沢美術工芸大学（金沢）
• [Presentation] マイナス荷電粒子優位な室内空気質の生体影響 (2013)
  • Author(s): 大槻剛巳
  • Organizer: 第８３回日本衛生学会学術総会
  • Place of Presentation: 金沢大学・金沢美術工芸大学（金沢）
• [Presentation] アスベスト曝露によるフォークヘッド転写因子Fox01の機能調節 (2012)
  • Author(s): 松崎秀紀
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都大学(京都)
  • Year and Date: 2012-03-25
• [Presentation] 石綿長期曝露T細胞株MT-2細胞における細胞周期変化の解析 (2012)
  • Author(s): 李順姫
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都大学(京都)
  • Year and Date: 2012-03-25
• [Presentation] クリソタイル継続曝露に伴うHTLV-1不死化多クローン性T細胞株の蛋白発現変化 (2012)
  • Author(s): 大槻剛巳
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都大学(京都)
  • Year and Date: 2012-03-25
• [Presentation] カーボンナノチューブ曝露のNK細胞機能に対する石綿に類似した抑制的影響 (2012)
  • Author(s): 西村泰光
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都大学(京都)
  • Year and Date: 2012-03-25
• [Presentation] Effect of Asbestos on Transcription Factor Foxo1 (2012)
  • Author(s): Hidenori Matsuzaki
  • Organizer: 30^<th> International Congress on Occupational Health
  • Place of Presentation: カンクンセンター(メキシコ)
  • Year and Date: 2012-03-19
• [Presentation] Continuous exposure to asbestos to human T cell caused reduction of CXCR3, a chemokine receptor (2012)
  • Author(s): Takemi Otsuki
  • Organizer: 30^<th> International Congress on Occupational Health
  • Place of Presentation: カンクンセンター(メキシコ)
  • Year and Date: 2012-03-19
• [Presentation] Immunotoxicology of Asbestos : Asebstos enhances regulatory T cell function (2012)
  • Author(s): Takemi Otsuki
  • Organizer: 30^<th> International Congress on Occupational Health
  • Place of Presentation: カンクンセンター(メキシコ)
  • Year and Date: 2012-03-19
• [Presentation] Effects of asbestos exposure on induction of cytotoxic T lymphocytes in mixed lymphocyte reactions and cytotoxic potential of CD8+ lymphocytes in asbestos-exposed people (2012)
  • Author(s): Naoko Kumagai
  • Organizer: 30^<th> International Congress on Occupational Health
  • Place of Presentation: カンクンセンター(メキシコ)
  • Year and Date: 2012-03-19
• [Presentation] Suppressive effect of exposure to asbestos on cytotoxicity of human NK cells (2012)
  • Author(s): Yasumitsu Nishimura
  • Organizer: 30^<th> International Congress on Occupational Health
  • Place of Presentation: カンクンセンター(メキシコ)
  • Year and Date: 2012-03-19
• [Presentation] Effect of asbestos on forkhead transcription factors Fox01 in MT-2 Cells (2012)
  • Author(s): Hidenori Matsuzaki
  • Organizer: 51st Annual Meeting of the Society of Toxicology
  • Place of Presentation: モスコーンセンター(カリフォルニア、米国)
  • Year and Date: 2012-03-13
• [Presentation] IFN-Γ, GRANZYME B AND PERFORIN-POSITIVE CELLS OF CD8+ LYMPHOCYTES IN ASBESTOS-EXPOSED PEOPLE WITH PLEURAL PLAQUE (2012)
  • Author(s): Naoko Kumagai-Takei
  • Organizer: 51st Annual Meeting of the Society of Toxicology
  • Place of Presentation: モスコーンセンクー(カリフォルニア、米国)
  • Year and Date: 2012-03-13
• [Presentation] MULTI-WALLED CARBON NANOTUBES EXERT ASBESTOS-LIKE SUPPRESSIVE EFFECT ON NK CELLS DECREASED CYTOTOXICITY WITH ALTERED EXPRESSION OF NK CELL-ACTIVATING RECEPTORS (2012)
  • Author(s): Yasumitsu Nishimura
  • Organizer: 51st Annual Meeting of the Society of Toxicology
  • Place of Presentation: モスコーンセンクー(カリフォルニア、米国)
  • Year and Date: 2012-03-13
• [Presentation] Continuous activation of responder T cells and regulatory T cells caused by silica exposure induce dysregulation of autoimmunity (2012)
  • Author(s): Takemi Otsuki
  • Organizer: 51st Annual Meeting of the Society of Toxicology
  • Place of Presentation: モスコーンセンター(カリフォルニア、米国)
  • Year and Date: 2012-03-13
• [Presentation] CONTINUOUS EXPOSURE OF ASBESTOS ALTERS CELL CYCLE REGULATION IN MT-2 CELL (2012)
  • Author(s): Suni Lee
  • Organizer: 51st Annual Meeting of the Society of Toxicology
  • Place of Presentation: モスコーンセンター(カリフォルニア、米国)
  • Year and Date: 2012-03-13
• [Presentation] THE ROLE OF TRANSCRIPTION FACTOR FOXO1 IN ASBESTOS-INDUCED APOPTOSIS OF MT-2CELLS (2012)
  • Author(s): Matsuzaki, H
  • Organizer: 52nd Annual Meeting of theSociety of Toxicology
  • Place of Presentation: Henry B. Gonzalez ConventionCenter(米国)
• [Presentation] The role of forkhead transcription factor FoxO1 in regulation of MT-2 cells (2012)
  • Author(s): Matsuzaki, H
  • Organizer: 第41回日本免疫学会学術総会
  • Place of Presentation: 神戸国際会議場
• [Presentation] アスベスト長期曝露により誘導されるMT-2細胞の機能変化のメカニズムの解析 (2012)
  • Author(s): 松崎秀紀
  • Organizer: 第19回免疫毒性学会
  • Place of Presentation: 東京慈恵会医科大学
• [Presentation] アスベスト曝露によるフォークヘッド転写因子FoxO1の機能調節 (2012)
  • Author(s): 松崎秀紀
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都大学
• [Presentation] Effect of Asbestos onTranscription Factor Foxo1 (2012)
  • Author(s): Matsuzaki, H
  • Organizer: 30thinternational Congress onOccupational Health
  • Place of Presentation: Cancun Center(メキシコ)
• [Presentation] Effect of asbestos onforkhead transcription factors FoxO1 in MT-2 Cells (2012)
  • Author(s): Matsuzaki, H
  • Organizer: 51st Annual Meeting of the Society of Toxicology
  • Place of Presentation: Moscone Center(米国)
• [Presentation] アスベスト長期曝露により誘導されるMT-2細胞の機能変化のメカニズムの解析 (2012)
  • Author(s): 松崎秀紀
  • Organizer: 第１９回免疫毒性学会
  • Place of Presentation: 慈恵会医科大学（東京）
• [Presentation] 石綿の低濃度・長期曝露は制御性T細胞モデル株MT-2細胞において細胞周期を亢進する (2012)
  • Author(s): 李 順姫
  • Organizer: 第１９回免疫毒性学会
  • Place of Presentation: 慈恵会医科大学（東京）
• [Presentation] 胸膜プラーク陽性者と悪性中皮腫患者のCD8+リンパ球の機能解析 (2012)
  • Author(s): 武井直子
  • Organizer: 第１９回免疫毒性学会
  • Place of Presentation: 慈恵会医科大学（東京）
• [Presentation] 免疫学的所見に基づくアスベスト曝露者の病態解析と診断指標構築の試み (2012)
  • Author(s): 西村泰光
  • Organizer: 第１９回免疫毒性学会
  • Place of Presentation: 慈恵会医科大学（東京）
• [Presentation] ヒトT細胞株に対するクロシドライト（青石綿）およびクリソタイル（白石綿）の継続曝露によるアスベスト誘導アポトーシス抵抗性の獲得 (2012)
  • Author(s): 大槻 剛巳
  • Organizer: 第１９回免疫毒性学会
  • Place of Presentation: 慈恵会医科大学（東京）
• [Presentation] The role of forkhead transcription factor FoxO1 in regulation of MT-2 cells (2012)
  • Author(s): Matsuzaki Hidenori
  • Organizer: 第４１回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場（神戸）
• [Presentation] Continuous exposure of asbestos decreases FoxO1 expression and it may accelerate cell cycle progression in Treg model cell line MT-2 cell (2012)
  • Author(s): Lee Suni
  • Organizer: 第４１回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場（神戸）
• [Presentation] IFNg production and cytotocity CD8+ lymphocytes in patients with pleural plaque or malignant mesothelioma (2012)
  • Author(s): Kumagai-Takei Naoko
  • Organizer: 第４１回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場（神戸）
• [Presentation] Carbon nanotubes-indued decrease in cytotoxicity of NK cells with altered expression of NK cell-activating receptors (2012)
  • Author(s): Nishimura Yasumitsu
  • Organizer: 第４１回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場（神戸）
• [Presentation] Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite on a human T cell (2012)
  • Author(s): Otsuki Takemi
  • Organizer: 第４１回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場（神戸）
• [Presentation] フォークヘッド転写因子Fox01に対するアスベスト曝露の影響 (2011)
  • Author(s): 松崎秀紀
  • Organizer: 第18回日本免疫毒性学会学術大会
  • Place of Presentation: 千葉大学(千葉県)
  • Year and Date: 2011-09-08
• [Presentation] 石綿曝露下PBMC培養時のIL-12,IFN-γ,IL-17A産生量低下とNK細胞上NKp46発現量減少との関わり (2011)
  • Author(s): 西村泰光
  • Organizer: 第18回日本免疫毒性学会学術大会
  • Place of Presentation: 千葉大学(千葉県)
  • Year and Date: 2011-09-08
• [Presentation] 混合リンパ球培養法で誘導されたメモリーCTLの成熟・維持における石綿曝露影響 (2011)
  • Author(s): 熊谷直子
  • Organizer: 第18回日本免疫毒性学会学術大会
  • Place of Presentation: 千葉大学(千葉県)
  • Year and Date: 2011-09-08
• [Presentation] 白石綿慢性曝露はin vitroでヒト末梢CD4陽性T細胞のIL-17産生を誘導する (2011)
  • Author(s): 前田恵
  • Organizer: 第18回日本免疫毒性学会学術大会
  • Place of Presentation: 千葉大学(千葉県)
  • Year and Date: 2011-09-08
• [Presentation] マイナス荷電粒子優位な室内環境の免疫影響 (2011)
  • Author(s): 大槻剛巳
  • Organizer: 第18回日本免疫毒性学会学術大会
  • Place of Presentation: 千葉大学(千葉県)
  • Year and Date: 2011-09-08
• [Presentation] フォークヘッド転写因子FoxO1に対するアスベスト曝露の影響 (2011)
  • Author(s): 松崎秀紀
  • Organizer: 第18回日本免疫毒性学会学術大会
  • Place of Presentation: 千葉大学
• [Remarks]
  • URL: http://www.kawasaki-m.ac.jp/hygiene/index.htm