Study of mechanisms for nanoparticle-induced inflammation and the development of safety evaluation methods for inflammation-related diseases.

• Project/Area Number: 25460798
• 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: Sugiyama Jogakuen University (2014-2015); Mie University (2013)
• Principal Investigator: Tada-Oikawa Saeko 椙山女学園大学, 生活科学部, 講師 (90610585)
• Co-Investigator(Kenkyū-buntansha): ICHIHARA Gaku 東京理科大学, 薬学部薬学科, 教授 (90252238)
• Co-Investigator(Renkei-kenkyūsha): KUBO Masataka 三重大学, 大学院地域イノベーション学研究科, 教授 (70195494)
• 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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ナノ粒子 / 炎症反応 / 二酸化チタン / 酸化亜鉛 / IL-1β / IL-8 / スカベンジャーレセプター / ナノ材料 / インフラマソーム / マクロファージ / 炎症

Outline of Final Research Achievements

The present study was designed to determine the effects of five TiO2 particles of different crystal structures and sizes in human epithelial colorectal adenocarcinoma (Caco-2) cells and THP-1 monocyte-derived macrophages. Exposure of THP-1 macrophages to 50μg/mL of anatase (50nm) TiO2 particles increased IL-1β expression level, and exposure of Caco-2 cells to 50μg/mL of anatase (50nm) TiO2 particles also increased IL-8 expression. The results indicated that anatase TiO2 nanoparticles induced inflammatory responses compared with other types of TiO2　particles.
Moreover, we found that exposure to ZnO particles increased macrophage cholesterol uptake, which was mediated by an upregulation of membrane scavenger receptors of modified LDL. The results suggested that nanosized ZnO particles could potentially enhance atherosclerogenesis and accelerate foam cell formation.

Research Products

• [Journal Article] Titanium dioxide particle type and concentration influence the inflammatory response in Caco-2 cells (2016)
  • Author(s): Tada-Oikawa S, Ichihara G, Fukatsu H, Shimanuki Y, Tanaka N, Suzuki Y, Murakami M, Izuoka K, Chang J, Wu W, Yamada Y, Ichihara S
  • Journal Title: International Journal of Molecular Sciences Volume: 17 Issue: 4 Pages: 576-576
  • DOI: 10.3390/ijms17040576
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Zn(II) released from zinc oxide nano/micro particles suppresses vasculogenesis in human endothelial colony-forming cells (2015)
  • Author(s): Saeko Tada-Oikawa, Gaku Ichihara, Yuka Suzuki, Kiyora Izuoka, Wenting Wu, Yoshiji Yamada, Takashi Mishima, Sahoko Ichihara
  • Journal Title: Toxicology Reports Volume: 2 Pages: 692-701
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Copper Oxide Nanoparticles Reduce Vasculogenesis in Transgenic Zebrafish Through Down-Regulation of Vascular Endothelial Growth Factor Expression and Induction of Apoptosis. (2015)
  • Author(s): Chang J, Ichihara G, Shimada Y, Tada-Oikawa S, Kuroyanagi J, Zhang B, Suzuki Y, Sehsah R, Kato M, Tanaka T, Ichihara S.
  • Journal Title: J Nanosci Nanotechnol Volume: 15 Pages: 2140-2147
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] HPLC法によるアンジオテンシン変換酵素阻害活性の測定と各種スプラウトの阻害活性 (2015)
  • Author(s): 志村 亜希子 , 及川 佐枝子 , 江崎 秀男
  • Journal Title: 椙山女学園大学研究論集 自然科学篇 Volume: 46 Pages: 71-80
  • NAID: 120006348795
• [Journal Article] Reduced Coenzyme Q10 Decreases Urinary 8-Oxo-7,8-Dihydro-2'-Deoxyguanosine Concentrations in Healthy Young Female Subjects. (2015)
  • Author(s): Ito K, Watanabe C, Nakamura A, Oikawa-Tada S, Murata M.
  • Journal Title: J Med Food Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] Synergistic effect of exposure to zinc oxide nanoparticle on inflammatory response to bleomycin-induced pulmonary fibrosis in mice (2014)
  • Author(s): W. Wu, G. Ichihara, N. Hashimoto, Y. Hasegawa, Y. Hayashi, S. Tada-Oikawa, Y. Suzuki, J. Chang, M. Kato, CN. D'Alessandro-Gabazza, EC. Gabazza, S. Ichihara
  • Journal Title: Int J Mol Sci Volume: 16 Issue: 1 Pages: 660-676
  • DOI: 10.3390/ijms16010660
  • Peer Reviewed / Open Access
• [Journal Article] Zinc oxide nanoparticles induce migration and adhesion of monocytes to endothelial cells and accelerate foam cell formation. (2014)
  • Author(s): Suzuki Y, Tada-Oikawa S, Ichihara G, Yabata M, Izuoka K, Suzuki M, Sakai K, Ichihara S.
  • Journal Title: Toxicol Appl Pharmacol Volume: in press Issue: 1 Pages: 16-25
  • DOI: 10.1016/j.taap.2014.04.010
  • Peer Reviewed
• [Journal Article] Proteomic analysis of carbonylated proteins in the monkey substantia nigra after ischemia-reperfusion. (2014)
  • Author(s): Oikawa S, Kobayashi H, Kitamura Y, Zhu H, Obata K, Minabe Y, Dazortsava M, Ohashi K, Tada-Oikawa S, Takahashi H, Yata K, Murata M, Yamashima T.
  • Journal Title: Free Radic Res Volume: 48 Issue: 6 Pages: 694-705
  • DOI: 10.3109/10715762.2014.901509
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Identification of a glutamic acid repeat polymorphism of ALMS1 as a novel genetic risk marker for early-onset myocardial infarction by genome-wide linkage analysis. (2013)
  • Author(s): Ichihara S, Yamamoto K, Asano H, Nakatochi M, Sukegawa M, Ichihara G, Izawa H, Hirashiki A, Takatsu F, Umeda H, Iwase M, Inagaki H, Hirayama H, Sone T, Nishigaki K, Minatoguchi S, Cho MC, Jang Y, Kim HS, Yokota M. 他10名
  • Journal Title: Circ Cardiovasc Genet Volume: 6 Issue: 6 Pages: 569-578
  • DOI: 10.1161/circgenetics.111.000027
  • Peer Reviewed
• [Journal Article] Endocrine disruptors found in food contaminants enhance allergic sensitization through an oxidative stress that promotes the development of allergic airway inflammation. (2013)
  • Author(s): Kato T, Tada-Oikawa S, Wang L, Murata M, Kuribayashi K.
  • Journal Title: Toxicol Appl Pharmacol. Volume: 273 Issue: 1 Pages: 10-18
  • DOI: 10.1016/j.taap.2013.08.029
  • Peer Reviewed
• [Journal Article] Serial changes in adipocytokines and cardiac function in a rat model of the metabolic syndrome. (2013)
  • Author(s): Yamaguchi T, Kitamori K, Ichihara G, Suzuki Y, Ochiai M, Yamada Y, Tada-Oikawa S, Tsuchikura S, Yamori Y, Ichihara S.
  • Journal Title: Clin Exp Pharmacol Physiol Volume: 40 Issue: 7 Pages: 443-448
  • DOI: 10.1111/1440-1681.12107
  • Peer Reviewed
• [Presentation] MicroRNAs as biomarkers for cigarette smoking and atherosclerosis. (2015)
  • Author(s): Sahoko Ichihara, Yuka Suzuki, Saeko Tada-Oikawa, Yuka Yokoyama, Kiyora Izuoka, Lingyu Zhang, Cai Zong, Gaku Ichihara
  • Organizer: The Scientific Sessions of American Heart Association
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] Effects of nano-sized TiO2 on the adhesion of monocytes to endothelial cells. (2015)
  • Author(s): Yuka Suzuki, Gaku Ichihara, Saeko Tada-Oikawa, Kiyora Izuoka, Sahoko Ichihara
  • Organizer: MARINA-NanoVALID conference
  • Place of Presentation: Paris, France
  • Year and Date: 2015-09-29
  • Int'l Joint Research
• [Presentation] Smoking-induced atherosclerosis through impairment of endothelial progenitor cell function (2015)
  • Author(s): Sahoko Ichihara, Yuka Suzuki, Saeko Tada-Oikawa, Yuka Yokoyama, Kiyora Izuoka, Cai Zong, Gaku Ichihara
  • Organizer: 7th International Congress of Asia Society of Toxicology (ASIATOX 2015)
  • Place of Presentation: Jeju Island, Korea
  • Year and Date: 2015-06-23
  • Int'l Joint Research
• [Presentation] Effects of nano-sized TiO2 on the adhesion of monocytes toendothelial cells (2015)
  • Author(s): Yuka Suzuki, Gaku Ichihara, Saeko Tada-Oikawa, Toshihiko Murakami, TomokiFurutani, Kiyora Izuoka, Sahoko Ichihara
  • Organizer: 7th International Congress of Asia Society of Toxicology (ASIATOX 2015)
  • Place of Presentation: Jeju Island, Korea
  • Year and Date: 2015-06-23
  • Int'l Joint Research
• [Presentation] Single-wall or double-wall carbon nanotubes induce atherosclerosis progression in animal and culture models of atherosclerosis (2015)
  • Author(s): Sahoko Ichihara, Yuka Suzuki, Saeko Tada-Oikawa, Kiyora Izuoka, Cai Zong, Gaku Ichihara
  • Organizer: 7th International Congress of Asia Society of Toxicology (ASIATOX 2015)
  • Place of Presentation: Jeju Island, Korea
  • Year and Date: 2015-06-23
  • Int'l Joint Research
• [Presentation] Single-wall or double-wall carbon nanotubes induce atherosclerosis progression in animal and culture models of atherosclerosis (2015)
  • Author(s): Sahoko Ichihara, Yuka Suzuki, Saeko Tada-Oikawa, Kiyora Izuoka, Cai Zong, Gaku Ichihara
  • Organizer: SENN2015 Congress
  • Place of Presentation: Helsinki, Finland
  • Year and Date: 2015-04-12
  • Int'l Joint Research
• [Presentation] Single-wall or double-wall carbon nanotubes induce atherosclerosis progression in animal and culture models of atherosclerosis. (2015)
  • Author(s): Yuka Suzuki, Gaku Ichihara, Cai Zong, Saeko Tada-Oikawa, Kiyora Izuoka, Sahoko Ichihara
  • Organizer: The 54rd Annual Meeting of the Society of Toxicology
  • Place of Presentation: San Diego, California, USA
  • Year and Date: 2015-03-22 – 2015-03-26
• [Presentation] Smoking-induced atherosclerosis via impairment of endothelial progenitor cell function. (2015)
  • Author(s): Sahoko Ichihara Yuka Suzuki, Saeko Tada-Oikawa, Cai Zong, Gaku Ichihara
  • Organizer: The 54rd Annual Meeting of the Society of Toxicology
  • Place of Presentation: San Diego, California, USA, March 2015
  • Year and Date: 2015-03-22 – 2015-03-26
• [Presentation] 単球の血管内皮細胞への接着能に及ぼす酸化チタンナノ粒子の影響 (2015)
  • Author(s): 鈴木 悠加、市原 学、及川(多田) 佐枝子、村上 理彦、出岡 淑、市原 佐保子
  • Organizer: 第14回 分子予防環境医学研究会
  • Place of Presentation: 大阪市
  • Year and Date: 2015-02-13 – 2015-02-14
• [Presentation] Synergistic effect of exposure to zinc oxide nanoparticle on inflammatory response to bleomycin-induced pulmonary fibrosis in mice. (2014)
  • Author(s): Wenting Wu, Gaku Ichihara, Naozumi Hashimoto, Yoshinori Hasegawa, Yasuhiko Hayashi, Masashi Kato, Saeko Tada-Oikawa, Yuka Suzuki, Jie Chang, Corina N. D'Alessandro-Gabazza, Esteban C. Gabazza, Sahoko Ichihara
  • Organizer: フォーラム2014 衛生学・環境トキシコロジー
  • Place of Presentation: つくば市
  • Year and Date: 2014-09-19 – 2014-09-20
• [Presentation] ナノ酸化亜鉛が、ブレオマイシンによって誘導されるマウスの肺線維症に与える影響 (2014)
  • Author(s): 呉 文亭、市原 学、及川（多田） 佐枝子、鈴木 悠加、常 杰、橋本 直純、長谷川 好規、Corina GABAZZA、Esteban GABAZZA、市原 佐保子
  • Organizer: 第41回 日本毒性学会学術年会
  • Place of Presentation: 神戸市
  • Year and Date: 2014-07-02 – 2014-07-04
• [Presentation] 酸化亜鉛ナノ粒子の血管内皮前駆細胞に対する影響 (2014)
  • Author(s): 及川（多田） 佐枝子、市原 学、鈴木 悠加、出岡 淑、三島 隆、市原 佐保子
  • Organizer: 第84回 日本衛生学会学術総会
  • Place of Presentation: 岡山市
  • Year and Date: 2014-05-25 – 2014-05-27
• [Presentation] コホート研究による動脈硬化症の発症要因における喫煙の影響の検討 (2014)
  • Author(s): 市原 佐保子、及川（多田） 佐枝子、菅原 望、水野 章、山田 芳司
  • Organizer: 第84回日本衛生学会総会
  • Place of Presentation: 岡山市
  • Year and Date: 2014-05-25 – 2014-05-27
• [Presentation] ナノ酸化亜鉛が、ブレオマイシンによって誘導されるマウスの肺線維症に与える影響 (2014)
  • Author(s): 呉 文亭、市原 学、及川（多田） 佐枝子、鈴木 悠加、常 杰、橋本 直純、長谷川 好規、ガバザ コリナ、ガバザ エステバン、市原 佐保子
  • Organizer: 第84回日本衛生学会総会
  • Place of Presentation: 岡山市
  • Year and Date: 2014-05-25 – 2014-05-27
• [Presentation] 単層、二層カーボンナノチューブによる動脈硬化症への影響とその作用機序の検討 (2014)
  • Author(s): 鈴木 悠加、市原 学、宗 才、及川（多田） 佐枝子、出岡 淑、市原 佐保子
  • Organizer: 第84回日本衛生学会総会
  • Place of Presentation: 岡山市
  • Year and Date: 2014-05-25 – 2014-05-27
• [Presentation] Effects of pharyngeal aspiration exposure to zinc oxide nanoparticles on pulmonary fibrosis induced by bleomycin in mice (2014)
  • Author(s): Wenting Wu, Gaku Ichihara, Saeko Tada-Oikawa, Yuka Suzuki, Jie Chang, Naozumi Hashimoto, Yoshinori Hasegawa, Corina Gabazza, Esteban Gabazza, Sahoko Ichihara
  • Organizer: 第13回分子予防環境医学研究会
  • Place of Presentation: 和歌山市
• [Presentation] 単層、二層カーボンナノチューブによるアテローム性動脈硬化への影響とその作用機序の検討 (2014)
  • Author(s): 鈴木悠加、市原学、宗才、及川（多田）佐枝子、出岡淑、市原佐保子
  • Organizer: 第13回分子予防環境医学研究会
  • Place of Presentation: 和歌山市
• [Presentation] ナノ酸化亜鉛が、ブレオマイシンによって誘導されるマウスの肺線維症に与える影響 (2013)
  • Author(s): 呉雯婷、市原学、及川（多田）佐枝子、鈴木悠加、常杰、橋本直純、長谷川好規、ガバザコリナ、ガバザエステバン、市原佐保子
  • Organizer: 第86回日本産業衛生学会学術総会
  • Place of Presentation: 松山市
• [Presentation] ゼブラフィッシュを用いたナノ酸化金属の血管新生に対する影響の検討 (2013)
  • Author(s): 常杰、市原学、及川（多田）佐枝子、島田康人、田中利男、市原佐保子
  • Organizer: 第86回日本産業衛生学会
  • Place of Presentation: 松山市
• [Presentation] ゼブラフィッシュを用いたナノ酸化金属の血管新生に対する影響の検討 (2013)
  • Author(s): 常杰、市原学、及川（多田）佐枝子、島田康人、田中利男、市原佐保子
  • Organizer: 第40回日本毒性学会学術年会
  • Place of Presentation: 千葉市
• [Presentation] The effects of pharyngeal aspiration exposure to zinc oxide nanoparticles on pulmonary fibrosis induced by bleomycin in mice (2013)
  • Author(s): Wenting Wu,Gaku Ichihara,Saeko Tada-Oikawa,Yuka Suzuki,Jie Chang,Naozumi Hashimoto,Yoshimori Hasegawa,Corina Gabazza,Esteban Gabazza and Sahoko Ichihara
  • Organizer: 日本産業衛生学会 第41回 産業中毒・生物学的モニタリング研究会
  • Place of Presentation: 大阪市
• [Presentation] Cytotoxicity induced by nano-sized TiO2 in human monocytic leukemia cells and colon cancer cells. (2013)
  • Author(s): Saeko Tada-Oikawa, Gaku Ichihara, Yuka Suzuki, Kiyora Izuoka, Sahoko Ichihara
  • Organizer: The 6th International Symposium on Nanotechnology, Occupational and Environmental Health; NanOEH6（第6回国際ナノテクノロジー労働環境衛生シンポジウム）
  • Place of Presentation: 名古屋市
• [Presentation] Zinc oxide nanoparticles induce cytotoxicity and apoptosis in humanendothelial colony-forming cells (2013)
  • Author(s): Saeko Tada-Oikawa, Gaku Ichihara, Yuka Suzuki, Kiyora Izuoka, Kiyoshi Sakai, Sahoko Ichihara
  • Organizer: The 6th International Symposium on Nanotechnology, Occupational and Environmental Health; NanOEH6（第6回国際ナノテクノロジー労働環境衛生シンポジウム）
  • Place of Presentation: 名古屋市
• [Presentation] Cardiovascular Effects of Manufactured Nanomaterials (2013)
  • Author(s): Sahoko Ichihara, Yuka Suzuki, Saeko Tada-Oikawa, Kiyora Izuoka, Cai Zong, Gaku Ichihara.
  • Organizer: 第23回日本MRS年次大会
  • Place of Presentation: 横浜市
• [Book] 公衆栄養学 第4版 (2016)
  • Author(s): 古畑公・松村康弘・鈴木三枝 編著／ 中嶋加代子・髙野美奈子・本田佳代子・髙松まり子・大木和子・及川佐枝子・今井具子・吉野佳織・岡田文江・小林陽子・藤澤由美子・高橋佳子
  • Total Pages: 240
  • Publisher: 光生館