アスベスト発癌に影響する免疫動態の解明

2010 年度 研究成果報告書

• 研究課題/領域番号: 20390178
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 衛生学
• 研究機関: 川崎医科大学
• 研究代表者: 大槻 剛巳 川崎医科大学, 医学部, 教授 (40160551)
• 研究分担者: 西村 泰光 川崎医科大学, 医学部, 准教授 (90360271) ; 前田 恵 川崎医科大学, 医学部, 助教 (20434988) ; 熊谷 直子 川崎医科大学, 医学部, 助教 (00509276) ; 村上 周子 川崎医科大学, 医学部, 助教 (50454848)
• 研究期間 (年度): 2008 – 2010
• キーワード: アスベスト / 珪酸 / 免疫担当細胞 / 腫瘍免疫 / 発癌

研究概要

2005年のクボタショック以来アスベスト曝露による悪性腫瘍の発生が問題となっているが,アスベスト曝露の免疫影響が腫瘍発生の素地を形成する可能性を考え検討してきた。その結果,実験系での免疫担当細胞(細胞株や健常人からの新鮮採取細胞)へのアスベスト曝露によって腫瘍免疫の減衰を示唆する所見が得られてきた。今後はその動態を改善することによって予防的分子標的を同定するなどに応用したい。

研究成果

• [雑誌論文] Dysregulation of the Immune System Caused by Silica and Asbestos. (2010)
  • 著者名/発表者名: Maeda M, Nishimura Y, Kumagai N, Hayashi H, Hatayama T, Katoh M, Miyahara N, Yamamoto S, Otsuki T.
  • 雑誌名: J Immunotoxicol 7(4) ページ: 268-278
  • 査読あり
• [雑誌論文] Reductive alteration of the regulatory function of the CD4+CD25+ T cell fraction in silicosis patients. (2010)
  • 著者名/発表者名: Hayashi H, Miura Y, Maeda M, Murakami S, Kumagai N, Nishimura M, Kusaka M, Uragami K, Fujimoto W, Otsuki T.
  • 雑誌名: Int J Immunopathol Pharmacol 23(4) ページ: 1099-1109
  • 査読あり
• [雑誌論文] Peripheral regulatory T cell from silicosis patients is susceptible to CD95-mediated apoptosis. (2010)
  • 著者名/発表者名: Hayashi H.
  • 雑誌名: Kawasaki Med J 36(1) ページ: 13-21
  • 査読あり
• [雑誌論文] 珪酸・アスベストの免疫影響(ミニ特集:繊維・粒子状物質研究会(仙台) (2010)
  • 著者名/発表者名: 熊谷直子,西村泰光,前田恵,林宏明,大槻剛巳
  • 雑誌名: 日本衛生学会誌 64(4) ページ: 93-499
  • 査読あり
• [雑誌論文] 珪肺症例における自己免疫異常の検出-血清可溶性インターロイキン2受容体と可溶性CD40リガンドの濃度の意義- (2010)
  • 著者名/発表者名: 林宏明,西村泰光,前田恵,熊谷直子,村上周子,三浦由恵,草加勝康,浦上更三,大槻剛巳
  • 雑誌名: 日本職業・災害医学会会誌 58(2) ページ: 45-51
  • 査読あり
• [雑誌論文] Impairment in cytotoxicity and expression of NK-cell activating receptors on human NK cells following exposure to asbestos fibers. (2009)
  • 著者名/発表者名: Nishimura Y, Miura Y, Maeda M, Kumagai N, Murakami S, Hayashi H, Fukuoka K, Nakano T, Otsuki T.
  • 雑誌名: Int J Immunopathol Pharmacol 22(3) ページ: 579-90
  • 査読あり
• [雑誌論文] Decrease in phosphorylation of ERK following decreased expression of NK-cell activating receptors in human NK cell line exposed to asbestos. (2009)
  • 著者名/発表者名: Nishimura Y, Maeda M, Kumagai N, Hayashi H, Miura Y, Otsuki T.
  • 雑誌名: Int J Immunopathol Pharmacol 22(4) ページ: 879-88
  • 査読あり
• [雑誌論文] Soluble interleukin-2 receptor as an indicator of immunological disturbance found in silicosis patients (2009)
  • 著者名/発表者名: Hayashi H, Maeda M, Murakami S, Kumagai N, Chen Y, Hatayama T, Katoh M, Miyahara N, Yamamoto S, Yoshida Y, Nishimura Y, Kusaka M, Fujimoto W, Otsuki T.
  • 雑誌名: Int J Imminopathol Pharmacol 22(1) ページ: 53-62
  • 査読あり
• [雑誌論文] Is soluble CD40 ligand an indicator of immunopathological disturbance in silicosis patients? (2009)
  • 著者名/発表者名: Hayashi H, Nishimura Y, Maeda M, Murakami S, Kumagai N, ChenY, Kusaka M, Uragami K, Fujimoto W, Otsuki T.
  • 雑誌名: Kawasaki Med J 35(2) ページ: 129-138
  • 査読あり
• [雑誌論文] Cytokine alteration and speculated immunological patho physiology in silicosis and asbestos-related diseases. (2009)
  • 著者名/発表者名: Murakami S, Nishimura Y, Maeda M, Kumagai N, Hayashi H, Chen Y, Kusaka K, Kishimoto T, Otsuki T.
  • 雑誌名: Environ Health Prev Med 14(4) ページ: 216-222
  • 査読あり
• [雑誌論文] Decreased CXCR3 expression in CD4+ T cells exposed to asbestos or derived from asbestos-exposed patients.
  • 著者名/発表者名: Maeda M, Nishimura Y, Hayashi H, Kumagai N, Chen Y, Murakami S, Miura Y, Hiratsuka J, Kishimoto T, Otsuki T.
  • 雑誌名: Am J Resp Cell Mol Biol (in press)
  • 査読あり
• [雑誌論文] Reduction of CXCR3 in an in vitro model of continuous asbestos exposure on a human T-cell line, MT-2.
  • 著者名/発表者名: Maeda M, Nishimura Y, Hayashi H, Kumagai N, Chen Y, Murakami S, Miura Y, Hiratsuka J, Kishimoto T, Otsuki T.
  • 雑誌名: Am J Resp Cell Mol Biol (in press)
  • 査読あり
• [雑誌論文] Dysregulation of autoimmunity caused by silica exposure and alteration of Fas-mediated apoptosis in T lymphocytes derived from silicosis patients.
  • 著者名/発表者名: Otsuki T, Hayashi H, Nishimura Y, Hyodo F, Maeda M, Kumagai N, Miura Y, Kusaka M, Urakami K
  • 雑誌名: Int J Immunopath Pharmacol 24(1)(in press)
  • 査読あり
• [雑誌論文] Suppressive effect of asbestos on cytotoxicity of human NK cells.
  • 著者名/発表者名: Nishimura Y, Kumagai N, Maeda M, Hayashi H, Fukuoka K, nakano T, Miura Y, HIratsuka J, Otsuki T.
  • 雑誌名: Int J Immunopath Pharmacol 24(1)(in press)
  • 査読あり
• [学会発表] Continuous and low-dose exposure to asbestos enhances TGF-β1 production in a human adult T cell leukemia virus-immortalized T cell line, MT-2. (2011)
  • 著者名/発表者名: Otsuki T, Maeda M, Kumagai N, Miyahara N, Katoh M, Yamamoto S, hatayama T, Nishimura Y
  • 学会等名: The 50th Anniversary Annual Meating of Society of Toxicology (U.S.A.).
  • 発表場所: Walter E. Washington Convention Center, Washington D.C. U.S.A.
  • 年月日: 20110307-20110310
• [学会発表] Asbestos exposure causes decrease in production of cytokines related to Nk cell activation. (2011)
  • 著者名/発表者名: Nishimura Y, Kumagai N, Maeda M, Hayashi H, Otsuki T
  • 学会等名: The 50th Anniversary Annual Meating of Society of Toxicology (U.S.A.).
  • 発表場所: Walter E. Washington Convention Center, Washington D.C. U.S.A.
  • 年月日: 20110307-20110310
• [学会発表] Enhanced suppressive function on regulatory T cell-like cell line, MT-2, by continuous exposure to asbestos. (2011)
  • 著者名/発表者名: Maeda M, Chen Y, Nishimura Y, Kumagai N, Hayashi H, Miura Y, Otsuki T
  • 学会等名: The 50th Anniversary Annual Meating of Society of Toxicology (U.S.A.).
  • 発表場所: Walter E. Washington Convention Center, Washington D.C. U.S.A.
  • 年月日: 20110307-20110310
• [学会発表] Effect of asbestos exposure on production of cytokines, apoptosis, and cell prolifertion related with differentiation of human CTL. (2011)
  • 著者名/発表者名: Kumagai N, Nishimura Y, Maeda M, Hayashi H, Otsuki T
  • 学会等名: The 50th Anniversary Annual Meating of Society of Toxicology (U.S.A.).
  • 発表場所: Walter E. Washington Convention Center, Washington D.C. U.S.A.
  • 年月日: 20110307-20110310
• [学会発表] The effects of cntinuous long-term exposure to asbestos, chrysotile and crocidolite on HTLV=1 immortalized human T cell line, MT-2. (2010)
  • 著者名/発表者名: Otsuki T, Maeda M, Miura Y, Kumagai N, Hayashi H, Yamamoto S, Nishimura Y
  • 学会等名: The 10th International Congress of the iMiG (International Mesotheloma Interest Group)
  • 発表場所: Kyoto International Conference Center
  • 年月日: 20100830-20100902
• [学会発表] Decrease in NKp46 in NK cells upon exposure to asbestos, a possible marker tomonitor anti-tumor immunity. (2010)
  • 著者名/発表者名: Nishimura Y, Kumagai N, Maeda M, Hayashi H, Kishimoto T, Otsuki T
  • 学会等名: The 10th International Congress of the iMiG (International Mesotheloma Interest Group)
  • 発表場所: Kyoto International Conference Center
  • 年月日: 20100830-20100902
• [学会発表] Human MT-2 cell line displays enhanced suppressive function by chronic exposure to asbestos. (2010)
  • 著者名/発表者名: Maeda M, Nishimura Y, Kumagai N, Hayashi H, Miura Y, Otsuki T
  • 学会等名: The 10th International Congress of the iMiG (International Mesotheloma Interest Group)
  • 発表場所: Kyoto International Conference Center
  • 年月日: 20100830-20100902
• [学会発表] Suppressive effects of asbestos-exposure on the differentiation of human cytotoxic T lymphocytes, accompanied with decrease in IFN-γ and TNF-α. (2010)
  • 著者名/発表者名: Kumagai N, Nishimura Y, Maeda M, Hayashi H, Kishimoto T, Otsuki T
  • 学会等名: The 10th International Congress of the iMiG (International Mesotheloma Interest Group)
  • 発表場所: Kyoto International Conference Center
  • 年月日: 20100830-20100902
• [学会発表] Decreased cytotoxity of human NK cells with low expression of NK cell-activating receptors upon exposure to asbestos, related with malignant mesotheioma. (2010)
  • 著者名/発表者名: Nishimura Y, Kumagai N, Maeda M, Hayashi H, fukuoka K, Nakano T, Kishimoto T, Otsuki T
  • 学会等名: 14th International Congress of Immunology
  • 発表場所: Kobe International Exhibition Hall
  • 年月日: 20100823-20100827
• [学会発表] Decreased induction of human CTL upon exposure to asbestos fibers (2010)
  • 著者名/発表者名: Kumagai N, Nishimura Y, Maeda M, Hayashi H, Otsuki T.
  • 学会等名: 14th International Congress of Immunology
  • 発表場所: Kobe International Exhibition Hall
  • 年月日: 20100823-20100827
• [学会発表] REduced alteration of the regulatory function of CD4+25+ T cell fraction in silicosis patients. (2010)
  • 著者名/発表者名: Hayashi H, Maeda M, Nishimura Y, Kumagai N, Miura Y, Otsuki T.
  • 学会等名: 14th International Congress of Immunology
  • 発表場所: Kobe International Exhibition Hall
  • 年月日: 20100823-20100827
• [学会発表] Alteration of cellular characteristics of HTLV-1 immortalized human T cell line, MT-2, by continuous long-term exposre to asbestos, chrysotile and crocidolite. (2010)
  • 著者名/発表者名: Otsuki T, Miura Y, Maeda M, Kumagai N, Hayahsi H, Nishimura Y
  • 学会等名: 14th International Congress of Immunology
  • 発表場所: Kobe International Exhibition Hall
  • 年月日: 20100823-20100827
• [学会発表] Relevance of chemokine receptor CXCR3 in asbestos-related diseases. (2010)
  • 著者名/発表者名: Maeda M, Nishimura Y, Kumagai N, Hayashi H, Miura Y, Kishimoto T, Otsuki T
  • 学会等名: 14th International Congress of Immunology
  • 発表場所: Kobe International Exhibition Hall
  • 年月日: 20100823-20100827
• [学会発表] Decreased Cytotoxicity of NK Cells with Low NKp46 Caused by Exposure to Asbestos, Observed in Patients with Mesothelioma. (2010)
  • 著者名/発表者名: Nishimura Y, Kumagai N, Maeda M, Hayashi H, Kishimoto T, Otsuki T
  • 学会等名: The 21st Japan China Korea Joint Conference on Occupational Health.
  • 発表場所: Tochigi-ken Sogo Bunka Center, Utsunomiya, JAPAN
  • 年月日: 20100610-20100612
• [学会発表] Exposure to Asbestos Suppressed the Differentiation of Human Cytotoxic T Lymphocytes. (2010)
  • 著者名/発表者名: Kumagai N, Nishimura Y, Maeda M, Hayashi H, Otsuki T
  • 学会等名: The 21st Japan China Korea Joint Conference on Occupational Health.
  • 発表場所: Tochigi-ken Sogo Bunka Center, Utsunomiya, JAPAN
  • 年月日: 20100610-20100612
• [学会発表] Application of CXCR3 expression in CD4+ T cells to the diagnosis of asbestos-related diseases. (2010)
  • 著者名/発表者名: Maeda M, Nishimura Y, Kumagai N, Hayashi H, Miura Y, Kishimoto T, Otsuki T
  • 学会等名: The 21st Japan China Korea Joint Conference on Occupational Health.
  • 発表場所: Tochigi-ken Sogo Bunka Center, Utsunomiya, JAPAN
  • 年月日: 20100610-20100612
• [学会発表] Immunological effects of silica and asbestos. (2010)
  • 著者名/発表者名: Otsuki T, Maeda M, Miura Y, Hayashi H, Kumagai N, Fukuoka K, Nakano T, Kishimoto T, Kusaka M, Uragami K, Nishimura Y.
  • 学会等名: ISOEAID'10 in KYOTO (International symposium on Occupational and Environmental Allergy and Immune Diseases 2010 in KYOTO (Local Organizer: Otsuki T)
  • 発表場所: KYODAI-KAIKAN (Kyoto, Japan)
  • 年月日: 20100407-20100409
• [学会発表] Suppressive effect of asbestos on cytotoxicity of human NK cells. (2010)
  • 著者名/発表者名: Nishimura Y, Kumagai N, Maeda M, Hayashi H, Fukuoka K, Nakano T, Kishimoto T, Otsuki T
  • 学会等名: ISOEAID'10 in KYOTO (International symposium on Occupational and Environmental Allergy and Immune Diseases 2010 in KYOTO (Local Organizer: Otsuki T)
  • 発表場所: KYODAI-KAIKAN (Kyoto, Japan)
  • 年月日: 20100407-20100409
• [学会発表] Analysis of immune index in asbesots-related disease. (2010)
  • 著者名/発表者名: Maeda M, Nishimura Y, Kumagai N< Hayashi H, Miura Y, Kishimoto T, Otsuki T
  • 学会等名: ISOEAID'10 in KYOTO (International symposium on Occupational and Environmental Allergy and Immune Diseases 2010 in KYOTO (Local Organizer: Otsuki T)
  • 発表場所: KYODAI-KAIKAN (Kyoto, Japan)
  • 年月日: 20100407-20100409
• [学会発表] Differentiation into human cytotoxic T lymphocytes are suppressed under exposure to asbestos. (2010)
  • 著者名/発表者名: Kumagai N, Nishimura Y, Maeda M, Hayashi H, Otsuki T
  • 学会等名: ISOEAID'10 in KYOTO (International symposium on Occupational and Environmental Allergy and Immune Diseases 2010 in KYOTO (Local Organizer: Otsuki T)
  • 発表場所: KYODAI-KAIKAN (Kyoto, Japan)
  • 年月日: 20100407-20100409
• [学会発表] Effects of asbestos on T-lymphocytes and NK cells in the development of tumor immunity. (2010)
  • 著者名/発表者名: Otsuki T, Maeda M, Kumagai N, Hayashi H, Nishimura Y
  • 学会等名: The Society of Toxicology (SOT) The 49th Annual Meeting in Salt Lake City, Utah
  • 年月日: 20100307-20100311
• [学会発表] Asbestos-exposure causes suppressed expression of NKp46 with low cytotoxicity in NK cells, related with malignant mesothelioma. (2010)
  • 著者名/発表者名: Nishimura Y, Kumagai N, Maeda M, Hayashi H, Kishimoto Y, Otsuki T
  • 学会等名: The Society of Toxicology (SOT) The 49th Annual Meeting in Salt Lake City, Utah
  • 年月日: 20100307-20100311
• [学会発表] functional analysis of human CD4+ T cells with decreased CXCR3 expression by long-term, low-dose exposure to asbestos. (2010)
  • 著者名/発表者名: Maeda M, Nishimura Y, Kumagai N, Hayashi H, Miura Y, Kishimoto T, Otsuki T
  • 学会等名: The Society of Toxicology (SOT) The 49th Annual Meeting in Salt Lake City, Utah
  • 年月日: 20100307-20100311
• [学会発表] suppressive effects of asbestos-exposure on the differentiation into human cytotoxic T lymphocytes (2010)
  • 著者名/発表者名: Kumagai N, Nishimura Y, Maeda M, Hayashi H, Otsuki T
  • 学会等名: The Society of Toxicology (SOT) The 49th Annual Meeting in Salt Lake City, Utah
  • 年月日: 20100307-20100311
• [学会発表] Suppressive effect of asbestos-exposure on cytotoxicity of human NK cells, and the possibility of NKp46 as a marker to monitor immune status in people exposed to asbestos. (2009)
  • 著者名/発表者名: Nishimura Y, Maeda M, Kumagai N, Murakami S, Hayashi H, Kishimoto T, Fukuoka K, Nakano T, Otsuki T
  • 学会等名: 第2回日中石綿シンポジウム, New CEntury Zhijiang Resort Hangzhou
  • 発表場所: Hangzhou, China
  • 年月日: 20090417-20090418
• [学会発表] Immunotoxicological effects of asbestos on human T cells. (2009)
  • 著者名/発表者名: Otsuki T, Maeda M, Murakami S, Miura Y, Kumagai N, Chen Y, Hayashi H, Nakano T, Fukuoka K, Kishimoto T, Nishimura Y
  • 学会等名: The 48th Society of Toxicology (USA)
  • 発表場所: Baltimore Convention Center in Baltimore, Maryland
  • 年月日: 20090315-20090319
• [学会発表] Keynote Speach (3). Achivement of Research Project "Comprehensive approach on asbestos-related diseases (sponsered by SCFPST)" and immunological effects of asbestos. (2008)
  • 著者名/発表者名: Otsuki T.
  • 学会等名: AAI (Asian Asebestos Initiative) International Conference in Kitakyushu
  • 発表場所: Japan
  • 年月日: 20081001-20081003
• [学会発表] Immunological changes in mesothelioma patients and their experimental detection. (2008)
  • 著者名/発表者名: Otsuki T,Maeda M, Murakami S,Hayashi H, Kumagai N,Miura Y,Ying C,Kuribayashi K,Fukuoka K,Kishimoto T,Nakano T,Nishimura Y
  • 学会等名: Inetrnational Mesothelioma Interest Group. Congress 2008
  • 発表場所: Amsterdam
  • 年月日: 20080925-20080927
• [学会発表] Impairment in cytotoxicity and expression of NK-cell activating receptors on human NK cells caused by exposure to asbestos fibers. (2008)
  • 著者名/発表者名: Nishimura Y, Maeda M, Murakami S, Hayashi H, Miura Y, fukuoka K, Nakano T, Otsuki T
  • 学会等名: Inetrnational Mesothelioma Interest Group. Congress 2008
  • 発表場所: Amsterdam
  • 年月日: 20080925-20080927
• [学会発表] Down-regulation of chemokine receptor CXCR3 in peripheral T lymphocytes from patients with asbestos-related disease. (2008)
  • 著者名/発表者名: Maeda M, Nishimura Y, Murakami S, Kumagai N, Hayashi H, Ying C, Miura Y, Nakano T, Kishimoto T, Otsuki T
  • 学会等名: Inetrnational Mesothelioma Interest Group. Congress 2008
  • 発表場所: Amsterdam
  • 年月日: 20080925-20080927
• [図書] 平成20年度両備てい園記念財団研究所製金による研究報告書(アスベスト曝露が誘導するヒトT細胞のTGF-β産生促進と制御性T細胞の関連性 生物学に関する試験論叢 第25集) (2010)
  • 著者名/発表者名: 前田恵
  • 総ページ数: 135-144
• [図書] 住居医学(IV)(筏義人,吉田修(編著))(アスベストの免疫影響) (2010)
  • 著者名/発表者名: 大槻剛巳,西村泰光,前田恵,三浦由恵,熊谷直子,林宏明
  • 総ページ数: 93-113
  • 出版者: 米田出版 千葉県市川市
• [図書] Asbestos : Risks, Environment and Impact.(Eds : Antonio Soto, Gael Salazar)(Immunological effects of Asbestos. ISBN978-1-60692-053-4) (2009)
  • 著者名/発表者名: Otsuki T, Maeda M, Miura Y, Hayashi H, Murakami S, Kumagai N, Nishimura Y
  • 総ページ数: 185-193
  • 出版者: [○!C]2009 Nova Science Publishers, Inc.
• [図書] 炎症・再生医学事典(編:松島綱治,西脇徹)(アスベストーシス ISBN978-4-254-30099-4C3547) (2009)
  • 著者名/発表者名: 林宏明,西村泰光,前田恵,大槻剛巳
  • 総ページ数: 269-271
  • 出版者: 朝倉書店,東京
• [図書] Autoimmune Disorder/Book 1(Inech Open Access Publisher Immunological effects of silica and related dysregulation of autoimmunity. ISBN:978-953-308-70-9)
  • 著者名/発表者名: Kumagai N, Hayashi H, Maeda M, Miura Y, Nishimura Y, Fujimoto W, Otsuki T.
  • 出版者: (in press)
• [図書] Autoimmune Disorders : Symptoms, Diagnosis and Treatment.(Editors : Maria E. Petro)(Dysregulation of Autoimmunity Caused by Silica Exposure : Fas-Mediated Apoptosis in T Lymphocytes Derived from Silicosis Patients. ISBN:978-1-61761-698-3)
  • 著者名/発表者名: Hayashi H, Nishimura Y, Hyodo F, Maeda M, Kumagai N, Miura Y, Kusaka M, Uragami K, Otsuki T.
  • 総ページ数: 293-301
  • 出版者: Nova Science Publishers, Inc.. Hauppauge, NY
• [図書] 分子予防環境医(アスベストーシス,シリコーシス 松島綱治)
  • 著者名/発表者名: 西村泰光,大槻剛巳,前田恵,熊谷直子
  • 総ページ数: 691-702
  • 出版者: 本の泉社 東京
• [備考] 川崎医科大学衛生学教室HPに研究概要を紹介
  • URL: http://www.kawasaki-m.ac.jp/hygiene/