Investigation of immunological parameters related with malignant mesothelioma, based on study of asbestos-caused impairment in cytotoxicity of NK cells

• Project/Area Number: 22790550
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Hygiene
• Research Institution: Kawasaki Medical School
• Principal Investigator: NISHIMURA Yasumitsu 川崎医科大学, 医学部, 准教授 (90360271)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 産業衛生 / アスベスト / 悪性中皮腫 / NK細胞 / 抗腫瘍免疫

Research Abstract

The in vitro study showed that asbestos exposure caused the decreases in production of IL-12 by monocyte-lineage cells and IFN-γ and IL-17A by Th cells, related with low NKp46 on NK cells. The six-seventh patients with mesothelioma showed a higher value of the formula, calculated from multiple linear regression analysis of cytokine levels in blood, than healthy or pleural plaque-positive people, suggesting that such formula might be a new marker for mesothelioma.

Research Products

• [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] Asbestos induces reduction of tumor immunity (2011)
  • Author(s): Kumagai N, Maeda M, Chen Y, Mastuzaki H, Lee S, Nishimura Y, Hiratsuka J, Otsuki T.
  • Journal Title: Clin Devl Immunol 2011 Pages: 481439-481439
  • Peer Reviewed
• [Journal Article] Decreased CXCR3 expression in CD4+T cells exposed to asbestos or derived from asbestos-exposed patients (2011)
  • 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 Volume: 45(4) Pages: 795-803
  • Peer Reviewed
• [Journal Article] Reduction of CXCR3 in an in vitro model of continuous asbestos exposure on a human T-cell line, MT-2 (2011)
  • 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 Volume: 45(3) Pages: 470-9
  • Peer Reviewed
• [Journal Article] Suppressive effect of asbestos on cytotoxicity of human NK cells (2011)
  • 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 Volume: 24(1)
  • Peer Reviewed
• [Journal Article] 科学技術振興調整費「アスベスト関連疾患への総括的取り組み」班研究:成果報告-班研究の概要と登録事業,中皮腫細胞特性ならびにアスベストの免疫影響について- (2011)
  • Author(s): 大槻剛巳, 中野孝司, 長谷川誠紀, 岡田守人, 辻村亨, 関戸好孝, 豊國伸哉, 西本寛, 福岡和也, 田中文啓, 熊谷直子, 前田恵, 松崎秀紀, 李順姫, 西村泰光
  • Journal Title: 日本衛生学雑誌 Volume: 66(3) Pages: 543-552
  • NAID: 10029364173
  • 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
• [Journal Article] Suppressive effect of asbestos on cytotoxicity of human NK cells (2011)
  • Author(s): Yasumitsu Nishimura
  • Journal Title: International Journal of Immunopathology and pharmacology Volume: Vol.24 Pages: 5-10
  • Peer Reviewed
• [Journal Article] Dysregulation of autoimmunity caused by silica exposure and alteration of Fas-mediated apoptosis in T lymphocytes derived from silicosis patients (2011)
  • Author(s): Takemi Otsuki
  • Journal Title: International Journal of Immunopathology and pharmacology Volume: Vol.24 Pages: 11-16
  • Peer Reviewed
• [Journal Article] Decreased CXCR3 expression in CD4+ T cells exposed to asbestos or derived from asbestos-exposed patients (2011)
  • Author(s): Megumi Maeda
  • Journal Title: American Journal of Respiratory Cell and Molecular Biology Volume: (Epub ahead of print)
  • Peer Reviewed
• [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 Volume: 7(4) Pages: 268-278
  • Peer Reviewed
• [Journal Article] 珪酸・アスベストの免疫影響 (2010)
  • Author(s): 熊谷直子, 西村泰光, 前田恵, 林宏明, 大槻剛巳
  • Journal Title: 日本衛生学会誌ミニ特集:繊維・粒子状物質研究会(仙台) Volume: 64(4) Pages: 93-499
  • NAID: 10029363262
  • Peer Reviewed
• [Journal Article] Reduction of CXCR3 in an in vitro model of continuous asbestos exposure on a human T-cell line, MT-2 (2010)
  • Author(s): Megumi Maeda
  • Journal Title: American Journal of Respiratory Cell and Molecular Biology Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Dysregulation of the Immune System Caused by Silica and Asbestos (2010)
  • Author(s): Megumi Maeda
  • Journal Title: Journal of Immunotoxicology Volume: 7 Pages: 268-278
  • 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 Volume: 22(3) Pages: 579-90
  • Peer Reviewed
• [Journal Article] Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite on a human T cell
  • Author(s): Meada M, Yamamoto S, Chen Y, Kumagai-Takei N, Hayashi H, Matsuzaki H, Lee S, Hatayama T, Miyahara N, Katoh M, Hiratsuka J-i, Nishimura Y, Otsuki T.
  • Journal Title: Sci Tot Environ Volume: (in press)
  • Peer Reviewed
• [Presentation] Suppressive effect of exposure to asbestos on cytotoxicity of human NK cells (2012)
  • Author(s): Yasumitsu Nishimura
  • Organizer: The 30th International Congress on Occupational Health
  • Place of Presentation: Cancun Center, Convention & exhibition, (Cancun)
  • Year and Date: 2012-03-19
• [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: The 51st Annual meeting of Society of Toxicology
  • Place of Presentation: Moscone Convention Center (San Francisco)
  • Year and Date: 2012-03-13
• [Presentation] アスベスト関連疾患に関わる肺胞マクロファージとNK細胞の機能変化 (2012)
  • Author(s): 西村泰光
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都大学吉田キャンパス(百周年時計台記念館・吉田南構内4号館)
• [Presentation] Suppressive effect of exposure to asbestos on cytotoxicity of human NK cells. (2012)
  • Author(s): Nishimura Y.
  • Organizer: 30th ICOH(International Commision on Occupational Healtj)
  • Place of Presentation: Cancun Center, Convention & exhibition, Cancun Mexico
• [Presentation] NK細胞機能と血漿中サイトカイン濃度解析に基づく中皮腫診断指標構築の試み (2012)
  • Author(s): 西村泰光, 武井直子, 前田恵, 松崎秀紀, 李順姫, 岸本卓巳, 大槻剛巳
  • Organizer: 第11回分子予防環境医学研究会
  • Place of Presentation: 倉敷市民会館2階大会議室
• [Presentation] 悪性中皮腫および石綿曝露に関連する血漿サイトカイン動態の解析 (2011)
  • Author(s): 西村泰光, 熊谷直子, 松崎秀紀, 李順姫, 岸本卓巳, 大槻剛巳
  • Organizer: 第18回石綿・中皮腫研究会
  • Place of Presentation: 長崎大学医学部ポンぺ会館
  • Year and Date: 2011-10-08
• [Presentation] Asbestos exposure causes decrease in production of cytokines related to NK cell activation (2011)
  • Author(s): Yasumitsu Nishimura
  • Organizer: The 50th Anniversary Annual Meeting of Society of Toxicology
  • Place of Presentation: Washington Convention Center (Washington D.C.)
  • Year and Date: 2011-03-07
• [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.
• [Presentation] 血漿中サイトカイン濃度解析による悪性中皮腫予防指標構築の試行 (2011)
  • Author(s): 西村泰光, 熊谷直子, 前田恵, 松崎秀紀, 李順姫, 岸本卓巳, 大槻剛巳
  • Organizer: 第55回中国四国合同日本産業衛生学会
  • Place of Presentation: 高知市総合あんしんセンター
• [Presentation] Low NKp46 on NK cells partially caused by decreased productions of IL12 (2011)
  • Author(s): Nishimura Y, Kumagai N, Maeda M, Lee S, Matsuzaki H, Otsuki T.
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ
• [Presentation] 石綿曝露下RBMC培養時のIL-12, IFN-γ, IL-17A産生量低下とNK細胞上NKp46発言量低下との関わり (2011)
  • Author(s): 西村泰光, 熊谷直子, 前田恵, 松崎秀紀, 李順姫, 大槻剛巳
  • Organizer: 第18回日本免疫毒性学会
  • Place of Presentation: 千葉大学けやき会館
• [Presentation] 石綿曝露時NK細胞機能の解析結果に基づく中皮腫予防に向けた抗腫瘍免疫機能評価の試行 (2011)
  • Author(s): 西村泰光, 熊谷直子, 前田恵, 松崎秀紀, 李順姫, 岸本卓巳, 大槻剛巳
  • Organizer: がん予防大会2011京都(第18回日本がん予防学会,第34回日本がん疫学・分子疫学研究会)
  • Place of Presentation: 京都府立医科大学図書館ホール
• [Presentation] Decreased productions of IL-12, IFN-・and IL-17A relevant to low NKp46 on NK cells in the culture of PBMCs upon exposure to asbestos 1JSICR-MMCB2011 (2011)
  • Author(s): Nishimura Y, Kumagai N, maeda M, Mastuzaki H, Lee S, Otsuki T.
  • Organizer: 第76回日本インターフェロン・サイトカイン学会.第19回マクロファージ分子細胞生物学国際シンポジウム.合同開催国際会議
  • Place of Presentation: ANA Gate Hiotel Osaka, Japan
• [Presentation] 石綿曝露下のPBMC由来IL-12, TNF-α, IFN-γ, IL-17A濃度低下とNK細胞上NKp46発現低下との関わり (2011)
  • Author(s): 西村泰光, 熊谷直子, 前田恵, 大槻剛巳
  • Organizer: 第84回日本産業衛生学会
  • Place of Presentation: シーサイドホテル芝弥生,ニューピアホール,ホテルアジュール竹芝,東京都立産業貿易センター浜松町館
• [Presentation] 石綿曝露時NK傷害性低下に関わるサイトカイン産生プロファイルの解析 (2011)
  • Author(s): 西村泰光, 熊谷直子, 前田恵, 大槻剛巳
  • Organizer: 第81回日本衛生学会学術総会
• [Presentation] 石綿曝露下のNK細胞機能低下に介在する作用機上の解析 (2010)
  • Author(s): 西村泰光, 前田恵, 熊谷直子, 大槻剛巳
  • Organizer: 第17回石綿・中皮腫研究会
  • Place of Presentation: 埼玉医科大学川越ビル大会議室(埼玉)
  • Year and Date: 2010-10-16
• [Presentation] Decrease in NKp46 in NK cells upon exposure to asbestos, a possible marker to monitor anti-tumor immunity (2010)
  • Author(s): Yasumitsu Nishimura
  • Organizer: The 10th International Congress of the iMiG (International Mesothelioma Interest Group)
  • Place of Presentation: Kyoto International Conference Center (Kyoto)
  • Year and Date: 2010-09-02
• [Presentation] Decreased cytotoxicity of human NK cells with low expression of NK cell-activating receptors upon exposure to asbestos, related with malignant mesothelioma (2010)
  • Author(s): Yasumitsu Nishimura
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe International Exhibition Hall (Kobe)
  • Year and Date: 2010-08-23
• [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) Annual Meeting
  • Place of Presentation: Salt Lake City
  • Year and Date: 2010-07-11
• [Presentation] K細胞障害性低下に関連した石綿曝露下PBMC培養時サイトカイン産生プロファイルの変化 (2010)
  • Author(s): 西村泰光, 熊谷直子, 前田恵, 林宏明, 大槻剛巳
  • Organizer: 第51回日本肺癌学会
  • Place of Presentation: 広島国際会議場・ANAクラウンプラザホテル広島
• [Presentation] 石綿曝露時NK細胞上NKp46低下に関連するサイトカイン産生の変化および単球系細胞の減少 (2010)
  • Author(s): 西村泰光, 熊谷直子, 前田恵, 林宏明, 大槻剛巳
  • Organizer: 第17回日本免疫毒性学会学術大会
  • Place of Presentation: 独立行政法人国立環境研究所大山記念ホール
• [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
• [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
• [Presentation] アスベスト曝露影響を測る免疫関連遺伝子の同定,新規診断法開発への試行 (2010)
  • Author(s): 西村泰光
  • Organizer: バイオアカデミックフォーラム/バイオテクノロジー国際会議/国際バイオエキスポ
  • Place of Presentation: 東京ビッグサイト
• [Presentation] アスベスト曝露下NK細胞機能低下に関わるサイトカイン産生量の変化 (2010)
  • Author(s): 西村泰光、熊谷直子、前田恵、林宏明、大槻剛巳
  • Organizer: 第75回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 北九州国際会議場
• [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
• [Presentation] 石綿曝露によるNK細胞上NKp46発現量低下における非リンパ系細胞の関わり (2010)
  • Author(s): 西村泰光, 熊谷直子, 前田恵, 林宏明, 岸本卓巳, 大槻剛巳
  • Organizer: 第83回日本産業衛生学会
  • Place of Presentation: フェニックスプラザ(福井市),福井県国際交流会館
• [Presentation] 石綿曝露によるNK細胞上NKp46発現量低下におけるサイトカインの関与 (2010)
  • Author(s): 西村泰光.熊谷直子, 前田恵, 林宏明, 大槻剛巳
  • Organizer: 第80回日本衛生学会学術総会
  • Place of Presentation: 仙台国際センター
• [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: International symposium on Occupational and Environmental Allergy and Immune Diseases 2010 in KYOTO
  • Place of Presentation: Kyoto, Japan
• [Book] Effect of asbestos on anti-tumor immunity and immunological alteration in patients with mesothelioma. In : Malignant Mesothelioma(Editors : Belli C.) (2012)
  • Author(s): Yasumitsu Nishimura
  • Publisher: InTech d.o.o.(In press)
• [Book] FACSによる検出法1細胞膜の抗原性in実験医学別冊現象を見抜き検出できる!細胞死実験プロトコール (2011)
  • Author(s): 山村真弘, 西村泰光, 刀祢重信, 小路武彦
  • Publisher: 羊土社
• [Book] Dysregulation of Autoimmunity Caused by Silica Exposure : Fas-Mediated Apoptosis in T Lymphocytes Derived from Silicosis Patients. IN. Autoimmune Disorders : Symptoms, Diagnosis and Treatment. Editors : Maria E.Petro (2011)
  • Author(s): Hiroaki Hayashi
  • Publisher: Nova Science Publishers, Inc.
• [Book] アスベストーシス,シリコーシス. In分子予防環境医学 (2010)
  • Author(s): 西村泰光, 大槻剛巳, 前田恵, 熊谷直子
  • Publisher: 本の泉社
• [Book] 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
  • Publisher: 米田出版
• [Book] アスベストーシス,シリコーシス.In分子予防環境医.松島綱治(編) (2010)
  • Author(s): 西村泰光
  • Publisher: 本の泉社
• [Book] アスベストの免疫影響.in住居医学(IV).筏義人,吉田修(編) (2010)
  • Author(s): 大槻剛巳
  • Publisher: 米田出版