Anaylisis of immunological alterations affecting asbestos-induced carcinogenesis

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390178
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hygiene
• Research Institution: Kawasaki Medical School
• Principal Investigator: OTSUKI Takemi Kawasaki Medical School, 医学部, 教授 (40160551)
• Co-Investigator(Kenkyū-buntansha): NISHIMURA Yasumitsu 川崎医科大学, 医学部, 准教授 (90360271) ; MAEDA Megumi 川崎医科大学, 医学部, 助教 (20434988) ; KUMAGAI Naoko 川崎医科大学, 医学部, 助教 (00509276) ; MURAKAMI Shuko 川崎医科大学, 医学部, 助教 (50454848)
• Project Period (FY): 2008 – 2010
• Keywords: アスベスト / 珪酸 / 免疫担当細胞 / 腫瘍免疫 / 発癌

Research Abstract

Since so-called "Kubota-Shock" in 2005, the issue regarding carcinogenesis among the patients exposed to asbestos has been medical and social problem. The aim of this project is to elucidate whether or not asbestos exposure affect on human immune system to tend to induce carcinogenesis. As the results, most of our findings indicate immune alteration caused by asbestos exposure using human cell lines and freshly isolated immune cells proceed to reducing tumor immunity. To find molecular preventive targets regarding immunological effects of asbestos should be performed in the future.

Research Products

• [Journal Article] Dysregulation of the Immune System Caused by Silica and Asbestos. (2010)
  • Author(s): Maeda M, Nishimura Y, Kumagai N, Hayashi H, Hatayama T, Katoh M, Miyahara N, Yamamoto S, Otsuki T.
  • Journal Title: J Immunotoxicol 7(4) Pages: 268-278
  • Peer Reviewed
• [Journal Article] Reductive alteration of the regulatory function of the CD4+CD25+ T cell fraction in silicosis patients. (2010)
  • Author(s): Hayashi H, Miura Y, Maeda M, Murakami S, Kumagai N, Nishimura M, Kusaka M, Uragami K, Fujimoto W, Otsuki T.
  • Journal Title: Int J Immunopathol Pharmacol 23(4) Pages: 1099-1109
  • Peer Reviewed
• [Journal Article] Peripheral regulatory T cell from silicosis patients is susceptible to CD95-mediated apoptosis. (2010)
  • Author(s): Hayashi H.
  • Journal Title: Kawasaki Med J 36(1) Pages: 13-21
  • Peer Reviewed
• [Journal Article] 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)
  • Author(s): 熊谷直子,西村泰光,前田恵,林宏明,大槻剛巳
  • Journal Title: 日本衛生学会誌 64(4) Pages: 93-499
  • Peer Reviewed
• [Journal Article] 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)
  • Author(s): 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
  • Journal Title: 日本職業・災害医学会会誌 58(2) Pages: 45-51
  • Peer Reviewed
• [Journal Article] Impairment in cytotoxicity and expression of NK-cell activating receptors on human NK cells following exposure to asbestos fibers. (2009)
  • Author(s): Nishimura Y, Miura Y, Maeda M, Kumagai N, Murakami S, Hayashi H, Fukuoka K, Nakano T, Otsuki T.
  • Journal Title: Int J Immunopathol Pharmacol 22(3) Pages: 579-90
  • Peer Reviewed
• [Journal Article] Decrease in phosphorylation of ERK following decreased expression of NK-cell activating receptors in human NK cell line exposed to asbestos. (2009)
  • Author(s): Nishimura Y, Maeda M, Kumagai N, Hayashi H, Miura Y, Otsuki T.
  • Journal Title: Int J Immunopathol Pharmacol 22(4) Pages: 879-88
  • Peer Reviewed
• [Journal Article] Soluble interleukin-2 receptor as an indicator of immunological disturbance found in silicosis patients (2009)
  • Author(s): 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.
  • Journal Title: Int J Imminopathol Pharmacol 22(1) Pages: 53-62
  • Peer Reviewed
• [Journal Article] Is soluble CD40 ligand an indicator of immunopathological disturbance in silicosis patients? (2009)
  • Author(s): Hayashi H, Nishimura Y, Maeda M, Murakami S, Kumagai N, ChenY, Kusaka M, Uragami K, Fujimoto W, Otsuki T.
  • Journal Title: Kawasaki Med J 35(2) Pages: 129-138
  • Peer Reviewed
• [Journal Article] Cytokine alteration and speculated immunological patho physiology in silicosis and asbestos-related diseases. (2009)
  • Author(s): Murakami S, Nishimura Y, Maeda M, Kumagai N, Hayashi H, Chen Y, Kusaka K, Kishimoto T, Otsuki T.
  • Journal Title: Environ Health Prev Med 14(4) Pages: 216-222
  • Peer Reviewed
• [Journal Article] Decreased CXCR3 expression in CD4+ T cells exposed to asbestos or derived from asbestos-exposed patients.
  • Author(s): Maeda M, Nishimura Y, Hayashi H, Kumagai N, Chen Y, Murakami S, Miura Y, Hiratsuka J, Kishimoto T, Otsuki T.
  • Journal Title: Am J Resp Cell Mol Biol (in press)
  • Peer Reviewed
• [Journal Article] Reduction of CXCR3 in an in vitro model of continuous asbestos exposure on a human T-cell line, MT-2.
  • Author(s): Maeda M, Nishimura Y, Hayashi H, Kumagai N, Chen Y, Murakami S, Miura Y, Hiratsuka J, Kishimoto T, Otsuki T.
  • Journal Title: Am J Resp Cell Mol Biol (in press)
  • Peer Reviewed
• [Journal Article] Dysregulation of autoimmunity caused by silica exposure and alteration of Fas-mediated apoptosis in T lymphocytes derived from silicosis patients.
  • Author(s): Otsuki T, Hayashi H, Nishimura Y, Hyodo F, Maeda M, Kumagai N, Miura Y, Kusaka M, Urakami K
  • Journal Title: Int J Immunopath Pharmacol 24(1)(in press)
  • Peer Reviewed
• [Journal Article] Suppressive effect of asbestos on cytotoxicity of human NK cells.
  • Author(s): Nishimura Y, Kumagai N, Maeda M, Hayashi H, Fukuoka K, nakano T, Miura Y, HIratsuka J, Otsuki T.
  • Journal Title: Int J Immunopath Pharmacol 24(1)(in press)
  • Peer Reviewed
• [Presentation] 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)
  • Author(s): Otsuki T, Maeda M, Kumagai N, Miyahara N, Katoh M, Yamamoto S, hatayama T, Nishimura Y
  • Organizer: The 50th Anniversary Annual Meating of Society of Toxicology (U.S.A.).
  • Place of Presentation: Walter E. Washington Convention Center, Washington D.C. U.S.A.
  • Year and Date: 20110307-20110310
• [Presentation] Asbestos exposure causes decrease in production of cytokines related to Nk cell activation. (2011)
  • Author(s): Nishimura Y, Kumagai N, Maeda M, Hayashi H, Otsuki T
  • Organizer: The 50th Anniversary Annual Meating of Society of Toxicology (U.S.A.).
  • Place of Presentation: Walter E. Washington Convention Center, Washington D.C. U.S.A.
  • Year and Date: 20110307-20110310
• [Presentation] Enhanced suppressive function on regulatory T cell-like cell line, MT-2, by continuous exposure to asbestos. (2011)
  • Author(s): Maeda M, Chen Y, Nishimura Y, Kumagai N, Hayashi H, Miura Y, Otsuki T
  • Organizer: The 50th Anniversary Annual Meating of Society of Toxicology (U.S.A.).
  • Place of Presentation: Walter E. Washington Convention Center, Washington D.C. U.S.A.
  • Year and Date: 20110307-20110310
• [Presentation] Effect of asbestos exposure on production of cytokines, apoptosis, and cell prolifertion related with differentiation of human CTL. (2011)
  • Author(s): Kumagai N, Nishimura Y, Maeda M, Hayashi H, Otsuki T
  • Organizer: The 50th Anniversary Annual Meating of Society of Toxicology (U.S.A.).
  • Place of Presentation: Walter E. Washington Convention Center, Washington D.C. U.S.A.
  • Year and Date: 20110307-20110310
• [Presentation] The effects of cntinuous long-term exposure to asbestos, chrysotile and crocidolite on HTLV=1 immortalized human T cell line, MT-2. (2010)
  • Author(s): Otsuki T, Maeda M, Miura Y, Kumagai N, Hayashi H, Yamamoto S, Nishimura Y
  • Organizer: The 10th International Congress of the iMiG (International Mesotheloma Interest Group)
  • Place of Presentation: Kyoto International Conference Center
  • Year and Date: 20100830-20100902
• [Presentation] Decrease in NKp46 in NK cells upon exposure to asbestos, a possible marker tomonitor anti-tumor immunity. (2010)
  • Author(s): Nishimura Y, Kumagai N, Maeda M, Hayashi H, Kishimoto T, Otsuki T
  • Organizer: The 10th International Congress of the iMiG (International Mesotheloma Interest Group)
  • Place of Presentation: Kyoto International Conference Center
  • Year and Date: 20100830-20100902
• [Presentation] Human MT-2 cell line displays enhanced suppressive function by chronic exposure to asbestos. (2010)
  • Author(s): Maeda M, Nishimura Y, Kumagai N, Hayashi H, Miura Y, Otsuki T
  • Organizer: The 10th International Congress of the iMiG (International Mesotheloma Interest Group)
  • Place of Presentation: Kyoto International Conference Center
  • Year and Date: 20100830-20100902
• [Presentation] Suppressive effects of asbestos-exposure on the differentiation of human cytotoxic T lymphocytes, accompanied with decrease in IFN-γ and TNF-α. (2010)
  • Author(s): Kumagai N, Nishimura Y, Maeda M, Hayashi H, Kishimoto T, Otsuki T
  • Organizer: The 10th International Congress of the iMiG (International Mesotheloma Interest Group)
  • Place of Presentation: Kyoto International Conference Center
  • Year and Date: 20100830-20100902
• [Presentation] Decreased cytotoxity of human NK cells with low expression of NK cell-activating receptors upon exposure to asbestos, related with malignant mesotheioma. (2010)
  • Author(s): Nishimura Y, Kumagai N, Maeda M, Hayashi H, fukuoka K, Nakano T, Kishimoto T, Otsuki T
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe International Exhibition Hall
  • Year and Date: 20100823-20100827
• [Presentation] Decreased induction of human CTL upon exposure to asbestos fibers (2010)
  • Author(s): Kumagai N, Nishimura Y, Maeda M, Hayashi H, Otsuki T.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe International Exhibition Hall
  • Year and Date: 20100823-20100827
• [Presentation] REduced alteration of the regulatory function of CD4+25+ T cell fraction in silicosis patients. (2010)
  • Author(s): Hayashi H, Maeda M, Nishimura Y, Kumagai N, Miura Y, Otsuki T.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe International Exhibition Hall
  • Year and Date: 20100823-20100827
• [Presentation] 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)
  • Author(s): Otsuki T, Miura Y, Maeda M, Kumagai N, Hayahsi H, Nishimura Y
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe International Exhibition Hall
  • Year and Date: 20100823-20100827
• [Presentation] Relevance of chemokine receptor CXCR3 in asbestos-related diseases. (2010)
  • Author(s): Maeda M, Nishimura Y, Kumagai N, Hayashi H, Miura Y, Kishimoto T, Otsuki T
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe International Exhibition Hall
  • Year and Date: 20100823-20100827
• [Presentation] Decreased Cytotoxicity of NK Cells with Low NKp46 Caused by Exposure to Asbestos, Observed in Patients with Mesothelioma. (2010)
  • Author(s): Nishimura Y, Kumagai N, Maeda M, Hayashi H, Kishimoto T, Otsuki T
  • Organizer: The 21st Japan China Korea Joint Conference on Occupational Health.
  • Place of Presentation: Tochigi-ken Sogo Bunka Center, Utsunomiya, JAPAN
  • Year and Date: 20100610-20100612
• [Presentation] Exposure to Asbestos Suppressed the Differentiation of Human Cytotoxic T Lymphocytes. (2010)
  • Author(s): Kumagai N, Nishimura Y, Maeda M, Hayashi H, Otsuki T
  • Organizer: The 21st Japan China Korea Joint Conference on Occupational Health.
  • Place of Presentation: Tochigi-ken Sogo Bunka Center, Utsunomiya, JAPAN
  • Year and Date: 20100610-20100612
• [Presentation] Application of CXCR3 expression in CD4+ T cells to the diagnosis of asbestos-related diseases. (2010)
  • Author(s): Maeda M, Nishimura Y, Kumagai N, Hayashi H, Miura Y, Kishimoto T, Otsuki T
  • Organizer: The 21st Japan China Korea Joint Conference on Occupational Health.
  • Place of Presentation: Tochigi-ken Sogo Bunka Center, Utsunomiya, JAPAN
  • Year and Date: 20100610-20100612
• [Presentation] Immunological effects of silica and asbestos. (2010)
  • Author(s): Otsuki T, Maeda M, Miura Y, Hayashi H, Kumagai N, Fukuoka K, Nakano T, Kishimoto T, Kusaka M, Uragami K, Nishimura Y.
  • Organizer: ISOEAID'10 in KYOTO (International symposium on Occupational and Environmental Allergy and Immune Diseases 2010 in KYOTO (Local Organizer: Otsuki T)
  • Place of Presentation: KYODAI-KAIKAN (Kyoto, Japan)
  • Year and Date: 20100407-20100409
• [Presentation] Suppressive effect of asbestos on cytotoxicity of human NK cells. (2010)
  • Author(s): Nishimura Y, Kumagai N, Maeda M, Hayashi H, Fukuoka K, Nakano T, Kishimoto T, Otsuki T
  • Organizer: ISOEAID'10 in KYOTO (International symposium on Occupational and Environmental Allergy and Immune Diseases 2010 in KYOTO (Local Organizer: Otsuki T)
  • Place of Presentation: KYODAI-KAIKAN (Kyoto, Japan)
  • Year and Date: 20100407-20100409
• [Presentation] Analysis of immune index in asbesots-related disease. (2010)
  • Author(s): Maeda M, Nishimura Y, Kumagai N< Hayashi H, Miura Y, Kishimoto T, Otsuki T
  • Organizer: ISOEAID'10 in KYOTO (International symposium on Occupational and Environmental Allergy and Immune Diseases 2010 in KYOTO (Local Organizer: Otsuki T)
  • Place of Presentation: KYODAI-KAIKAN (Kyoto, Japan)
  • Year and Date: 20100407-20100409
• [Presentation] Differentiation into human cytotoxic T lymphocytes are suppressed under exposure to asbestos. (2010)
  • Author(s): Kumagai N, Nishimura Y, Maeda M, Hayashi H, Otsuki T
  • Organizer: ISOEAID'10 in KYOTO (International symposium on Occupational and Environmental Allergy and Immune Diseases 2010 in KYOTO (Local Organizer: Otsuki T)
  • Place of Presentation: KYODAI-KAIKAN (Kyoto, Japan)
  • Year and Date: 20100407-20100409
• [Presentation] Effects of asbestos on T-lymphocytes and NK cells in the development of tumor immunity. (2010)
  • Author(s): Otsuki T, Maeda M, Kumagai N, Hayashi H, Nishimura Y
  • Organizer: The Society of Toxicology (SOT) The 49th Annual Meeting in Salt Lake City, Utah
  • Year and Date: 20100307-20100311
• [Presentation] Asbestos-exposure causes suppressed expression of NKp46 with low cytotoxicity in NK cells, related with malignant mesothelioma. (2010)
  • Author(s): Nishimura Y, Kumagai N, Maeda M, Hayashi H, Kishimoto Y, Otsuki T
  • Organizer: The Society of Toxicology (SOT) The 49th Annual Meeting in Salt Lake City, Utah
  • Year and Date: 20100307-20100311
• [Presentation] functional analysis of human CD4+ T cells with decreased CXCR3 expression by long-term, low-dose exposure to asbestos. (2010)
  • Author(s): Maeda M, Nishimura Y, Kumagai N, Hayashi H, Miura Y, Kishimoto T, Otsuki T
  • Organizer: The Society of Toxicology (SOT) The 49th Annual Meeting in Salt Lake City, Utah
  • Year and Date: 20100307-20100311
• [Presentation] suppressive effects of asbestos-exposure on the differentiation into human cytotoxic T lymphocytes (2010)
  • Author(s): Kumagai N, Nishimura Y, Maeda M, Hayashi H, Otsuki T
  • Organizer: The Society of Toxicology (SOT) The 49th Annual Meeting in Salt Lake City, Utah
  • Year and Date: 20100307-20100311
• [Presentation] 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)
  • Author(s): Nishimura Y, Maeda M, Kumagai N, Murakami S, Hayashi H, Kishimoto T, Fukuoka K, Nakano T, Otsuki T
  • Organizer: 第2回日中石綿シンポジウム, New CEntury Zhijiang Resort Hangzhou
  • Place of Presentation: Hangzhou, China
  • Year and Date: 20090417-20090418
• [Presentation] Immunotoxicological effects of asbestos on human T cells. (2009)
  • Author(s): Otsuki T, Maeda M, Murakami S, Miura Y, Kumagai N, Chen Y, Hayashi H, Nakano T, Fukuoka K, Kishimoto T, Nishimura Y
  • Organizer: The 48th Society of Toxicology (USA)
  • Place of Presentation: Baltimore Convention Center in Baltimore, Maryland
  • Year and Date: 20090315-20090319
• [Presentation] Keynote Speach (3). Achivement of Research Project "Comprehensive approach on asbestos-related diseases (sponsered by SCFPST)" and immunological effects of asbestos. (2008)
  • Author(s): Otsuki T.
  • Organizer: AAI (Asian Asebestos Initiative) International Conference in Kitakyushu
  • Place of Presentation: Japan
  • Year and Date: 20081001-20081003
• [Presentation] Immunological changes in mesothelioma patients and their experimental detection. (2008)
  • Author(s): Otsuki T,Maeda M, Murakami S,Hayashi H, Kumagai N,Miura Y,Ying C,Kuribayashi K,Fukuoka K,Kishimoto T,Nakano T,Nishimura Y
  • Organizer: Inetrnational Mesothelioma Interest Group. Congress 2008
  • Place of Presentation: Amsterdam
  • Year and Date: 20080925-20080927
• [Presentation] Impairment in cytotoxicity and expression of NK-cell activating receptors on human NK cells caused by exposure to asbestos fibers. (2008)
  • Author(s): Nishimura Y, Maeda M, Murakami S, Hayashi H, Miura Y, fukuoka K, Nakano T, Otsuki T
  • Organizer: Inetrnational Mesothelioma Interest Group. Congress 2008
  • Place of Presentation: Amsterdam
  • Year and Date: 20080925-20080927
• [Presentation] Down-regulation of chemokine receptor CXCR3 in peripheral T lymphocytes from patients with asbestos-related disease. (2008)
  • Author(s): Maeda M, Nishimura Y, Murakami S, Kumagai N, Hayashi H, Ying C, Miura Y, Nakano T, Kishimoto T, Otsuki T
  • Organizer: Inetrnational Mesothelioma Interest Group. Congress 2008
  • Place of Presentation: Amsterdam
  • Year and Date: 20080925-20080927
• [Book] 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)
  • Author(s): 前田恵
  • Total Pages: 135-144
• [Book] 住居医学(IV)(筏義人,吉田修(編著))(アスベストの免疫影響) (2010)
  • Author(s): 大槻剛巳,西村泰光,前田恵,三浦由恵,熊谷直子,林宏明
  • Total Pages: 93-113
  • Publisher: 米田出版 千葉県市川市
• [Book] Asbestos : Risks, Environment and Impact.(Eds : Antonio Soto, Gael Salazar)(Immunological effects of Asbestos. ISBN978-1-60692-053-4) (2009)
  • Author(s): Otsuki T, Maeda M, Miura Y, Hayashi H, Murakami S, Kumagai N, Nishimura Y
  • Total Pages: 185-193
  • Publisher: [○!C]2009 Nova Science Publishers, Inc.
• [Book] 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)
  • Author(s): 林宏明,西村泰光,前田恵,大槻剛巳
  • Total Pages: 269-271
  • Publisher: 朝倉書店,東京
• [Book] Autoimmune Disorder/Book 1(Inech Open Access Publisher Immunological effects of silica and related dysregulation of autoimmunity. ISBN:978-953-308-70-9)
  • Author(s): Kumagai N, Hayashi H, Maeda M, Miura Y, Nishimura Y, Fujimoto W, Otsuki T.
  • Publisher: (in press)
• [Book] 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)
  • Author(s): Hayashi H, Nishimura Y, Hyodo F, Maeda M, Kumagai N, Miura Y, Kusaka M, Uragami K, Otsuki T.
  • Total Pages: 293-301
  • Publisher: Nova Science Publishers, Inc.. Hauppauge, NY
• [Book] 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)
  • Author(s): 西村泰光,大槻剛巳,前田恵,熊谷直子
  • Total Pages: 691-702
  • Publisher: 本の泉社 東京
• [Remarks] 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/