Inflammatory responses triggered by inflammasome activation after exposure to carbon nanotubes

• Project/Area Number: 15K15236
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hygiene and public health
• Research Institution: Jichi Medical University (2017); Mie University (2015-2016)
• Principal Investigator: ICHIHARA Sahoko 自治医科大学, 医学部, 教授 (20378326)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 炎症 / ナノ素材 / 心血管系 / 安全性評価 / ナノ粒子 / 炎症反応 / インフラマソーム / 動脈硬化 / リスク評価

Outline of Final Research Achievements

Apolipoprotein E-deficient (ApoE-/-) mice treated with double wall carbon nanotubes (DWCNTs) at the high dose showed increased plaque area in the aorta by oil red O staining. The expression of NLRP3, which is a central constitutive factor of inflammasome, and the expression of inflammatory factors (VCAM-1, ICAM-1) and cytokine (MCP-1) were significantly increased in ApoE-/- mice treated with long DWCNTs at the high dose. Furthermore, in human umbilical vein endothelial cells (HUVECs) treated with the high dose of DWCNTs the level of cytokine (IL-1β) was significantly elevated. The results suggested that DWCNTs induced the formation of arteriosclerotic lesion due to enhancing inflammatory responses triggered by inflammasome activation.

Research Products

• [Journal Article] MicroRNAs as Potential Mediators for Cigarette Smoking Induced Atherosclerosis (2018)
  • Author(s): Yokoyama Yuka、Mise Nathan、Suzuki Yuka、Tada-Oikawa Saeko、Izuoka Kiyora、Zhang Lingyi、Zong Cai、Takai Akira、Yamada Yoshiji、Ichihara Sahoko
  • Journal Title: International Journal of Molecular Sciences Volume: 19 Issue: 4 Pages: 1097-1097
  • DOI: 10.3390/ijms19041097
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Proteomics analysis identified peroxiredoxin 2 involved in early-phase left ventricular impairment in hamsters with cardiomyopathy. (2018)
  • Author(s): Kuzuya K, Ichihara S, Suzuki Y, Inoue C, Ichihara G, Kurimoto S, Oikawa S.
  • Journal Title: PLoS One. Volume: 13 Issue: 2 Pages: e0192624-e0192624
  • DOI: 10.1371/journal.pone.0192624
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Exposure of Mice to 1,2-Dichloropropane Induces CYP450-Dependent Proliferation and Apoptosis of Cholangiocytes. (2018)
  • Author(s): Zong C, Zhang X, Huang C, Chang J, Garner E, Sakurai T, Kato M, Ichihara S, Ichihara G.
  • Journal Title: Toxicol Sci Volume: 162 Issue: 2 Pages: 559-69
  • DOI: 10.1093/toxsci/kfx272
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Epigenome-wide association of myocardial infarction with DNA methylation sites at loci related to cardiovascular disease. (2017)
  • Author(s): Nakatochi M, Ichihara S, Yamamoto K, Naruse K, Yokota S, Asano H, Matsubara T, Yokota M.
  • Journal Title: Clin. Epigenetics Volume: 9 Issue: 1 Pages: 54-54
  • DOI: 10.1186/s13148-017-0353-3
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease (2017)
  • Author(s): Morimoto T, Mineharu Y, Ono K, Nakatochi M, Ichihara S, Kabata R, Takagi Y, Cao Y, Zhao L, Kobayashi H, Harada K. H, Takenaka K, Funaki T, Yokota M, Matsubara T, Yamamoto K, Izawa H, Kimura T, Miyamoto S, Koizumi A
  • Journal Title: PLoS ONE Volume: 12 Issue: 4 Pages: e0175649-e0175649
  • DOI: 10.1371/journal.pone.0175649
  • NAID: 120006534994
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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] Preliminary characterization of a murine model for 1-bromopropane neurotoxicity: Role of cytochrome P450 (2016)
  • Author(s): C. Zong, C.E. Garner, C. Huang, X. Zhang, L. Zhang, J. Chang, S. Toyokuni, H. Ito, M. Kato, T. Sakurai, S. Ichihara, G. Ichihara
  • Journal Title: Toxicological Letters Volume: 258 Pages: 249-258
  • DOI: 10.1016/j.toxlet.2016.07.006
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of 4-week inhalation exposure to 1-bromopropane on blood pressure in rats (2016)
  • Author(s): Huang F, Ichihara S, Yamada Y, Banu S, Ichihara G
  • Journal Title: J Appl Toxicol Volume: 37 Issue: 3 Pages: 331-338
  • DOI: 10.1002/jat.3364
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of cytochrome P450s in the male reproductive toxicity of 1-bromopropane (2016)
  • Author(s): Zong C, Zhang X, Huang C, Chang J, Garner CE, Sakurai T, Kato M, Ichihara S, Ichihara G
  • Journal Title: Toxicology Research Volume: 5 Issue: 6 Pages: 1522-1529
  • DOI: 10.1039/c6tx00164e
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Single- and double-wall carbon nanotubes enhance atherosclerogenesis by promoting monocyte adhesion to endothelial cells and endothelial progenitor cell dysfunction (2016)
  • Author(s): Suzuki Y, Tada-Oikawa S, Hayashi Y, Izuoka K, Kataoka M, Ichikawa S, Wu W, Ichihara G, Ichihara S
  • Journal Title: Particle and Fibre Toxicology Volume: 13 Issue: 1 Pages: 54-54
  • DOI: 10.1186/s12989-016-0166-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Zn(II) released from zinc oxide nano/micro particles was involved in the attenuation of vasculogenesis in human endothelial colony-forming cells (2015)
  • Author(s): Tada-Oikawa S, Ichihara G, Suzuki Y, Izuoka K, Yamada Y, Mishima T, Ichihara S
  • Journal Title: Toxicology Reports Volume: 2 Pages: 692-701
  • Peer Reviewed
• [Presentation] カーボンナノチューブによる血管における炎症誘導機構の解明 (2018)
  • Author(s): 岩瀬優、鈴木悠加、出岡淑、宗才、市原学、市原佐保子
  • Organizer: 第17回分子予防環境医学研究会
• [Presentation] シリカナノ粒子の表面修飾とRAW264.7細胞応答との関係 (2017)
  • Author(s): 長田 百合果，渡邊 英里，ブラニッチ サンドラ，市原 佐保子，櫻井 敏博，鈴木 利宙，ボーランド ソニア，トラン ラン，安部 良，市原 学
  • Organizer: 第87回日本衛生学会学術総会
  • Place of Presentation: フェニックス・シーガイア・リゾート（宮崎県・宮崎市）
  • Year and Date: 2017-03-26
• [Presentation] 酸化チタンナノ粒子の物理化学的特性による血管内皮細胞への影響 (2017)
  • Author(s): 市原 佐保子, 鈴木 悠加, 古谷 知己, 出岡 淑, 渡邊 英里, 林田 有紗, 長田 百合果, 市原 学
  • Organizer: 第87回日本衛生学会学術総会
  • Place of Presentation: フェニックス・シーガイア・リゾート（宮崎県・宮崎市）
  • Year and Date: 2017-03-26
• [Presentation] Surface modifications of silica nanoparticles affect their uptake by the cells and subsequent pulmonary toxicity. (2017)
  • Author(s): Sandra Vranic, Eri Watanabe, Yurika Osada, Sahoko Ichihara, Wenting Wu, Toshihiro Sakurai, Toshihiro Suzuki, Ryo Abe, Sonia Boland, Lang Tran, Gaku Ichihara.
  • Organizer: 8th International Symposium on Nanotechnology, Occupational and Environmental Health
  • Int'l Joint Research
• [Presentation] シリカナノ粒子の表面修飾とRAW264.7細胞応答との関係 (2017)
  • Author(s): 長田 百合果, 渡邊 英里, Sandra VRANIC, 市原 佐保子, 櫻井 敏博, 鈴木 利宙,
  • Organizer: 第44回日本毒性学会学術年会
• [Presentation] Identification of smoking induced changes in DNA methylation in an epigenome wide scan. (2017)
  • Author(s): Sahoko Ichihara, Masahiro Nakatochi, Tastuaki Matsubara, Gaku Ichihara, Mitsuhiro Yokota , Ken Yamamoto.
  • Organizer: 10th International Symposium on Biological Monitoring in Occupational and Environmental Health
  • Int'l Joint Research
• [Presentation] 酸化チタンナノ粒子の物理化学的特性による影響 (2017)
  • Author(s): 林田 有紗, 市原 学, 渡辺 英里, 鈴木 悠加, 古谷 知己, 出岡 淑, 市原 佐保子
  • Organizer: 第 12 回ナノ・バイオメディカル学会
• [Presentation] Surface modifications of silica nanoparticles affect their uptake by the cells and subsequent pulmonary toxicity. (2016)
  • Author(s): Eri Watanabe, Sandra Vranic, Sahoko Ichihara, Wenting Wu, Yurika Osada, Toshihiro Sakurai, Sonja Boland, Lang Tran, Gaku Ichihara.
  • Organizer: 11th International Particle Toxicology Conference
  • Place of Presentation: Singapore, Republic of Singapore
  • Year and Date: 2016-09-26
  • Int'l Joint Research
• [Presentation] Effect of physicochemical characteristics of nano-sized TiO2 on adhesion of monocytes to endothelial cells. (2016)
  • Author(s): Sahoko Ichihara, Yuka Suzuki, Eri Watanabe, Arisa Hayashida, Yurika Osada, Tomoki Furutani, Kiyora Izuoka, Gaku Ichihara.
  • Organizer: 11th International Particle Toxicology Conference
  • Place of Presentation: Singapore, Republic of Singapore
  • Year and Date: 2016-09-26
  • Int'l Joint Research
• [Presentation] Effects of nano-sized TiO2 on the adhesion of monocytes to endothelial cells by the differences in the crystal structure and characteristics of the surface of nanoparticles. (2016)
  • Author(s): Gaku Ichihara, Yuka Suzuki, Eri Watanabe, Arisa Hayashida, Yurika Osada, Tomoki Furutani, Kiyora Izuoka, Sahoko Ichihara.
  • Organizer: 52nd European Congress of the European Societies of Toxicology
  • Place of Presentation: Seville, Spain
  • Year and Date: 2016-09-04
  • Int'l Joint Research
• [Presentation] マウスにおけるシリカナノ粒子の表面修飾と炎症誘導作用との関係 (2016)
  • Author(s): 渡邊 英里、ブラニッチ サンドラ、市原 佐保子、呉 文亭、鈴木 利宙、長田 百合果、張 霊逸、櫻井 敏博、ボーランド ソニア、トラン ラン、安部 良、市原 学
  • Organizer: 第44回産業中毒・生物学的モニタリング研究会
  • Place of Presentation: 東京理科大学森戸記念館（東京都・新宿区）
  • Year and Date: 2016-08-04
• [Presentation] 酸化チタンナノ粒子の物理化学的特性による血管内皮細胞への影響の検討 (2016)
  • Author(s): 市原佐保子、鈴木悠加、古谷知己、出岡淑、渡邊英里、林田有紗、長田百合香、市原学
  • Organizer: 第44回産業中毒・生物学的モニタリング研究会
  • Place of Presentation: 東京理科大学森戸記念館（東京都・新宿区）
  • Year and Date: 2016-08-04
• [Presentation] ナノマテリアル有害性評価と労働環境衛生学 (2016)
  • Author(s): 市原 学, 小林 隆弘, 市原 佐保子
  • Organizer: 第43回日本毒性学会学術年会
  • Place of Presentation: ウインクあいち（愛知県・名古屋市）
  • Year and Date: 2016-06-29
• [Presentation] 酸化チタンナノ粒子による血管内皮細胞への単球の接着能に対する影響 (2016)
  • Author(s): 市原 佐保子, 鈴木 悠加, 古谷 知己, 出岡 淑, 渡邊 英里, 林田 有紗, 長田 百合果, 市原 学
  • Organizer: 第43回日本毒性学会学術年会
  • Place of Presentation: ウインクあいち（愛知県・名古屋市）
  • Year and Date: 2016-06-29
• [Presentation] Surface modifications of silica nanoparticles affect their uptake by the cells and subsequent pulmonary toxicity. (2016)
  • Author(s): Gaku Ichihara, Sandra Vranic, Sahoko Ichihara, Wenting Wu, Eri Watanabe, Arisa Hayashida, Yurika Osada, Toshihiko Sakurai, Sonja Boland, Lang Tran.
  • Organizer: 8th International Nanotoxicology Congress
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 2016-06-01
  • Int'l Joint Research
• [Presentation] 吸引投与による多層カーボンナノチューブの影響とその作用機序の検討 (2016)
  • Author(s): 市原佐保子、鈴木悠加、呉文亭、出岡淑、伊東健、山本雅之、市原学
  • Organizer: 第86回日本衛生学会学術総会
  • Place of Presentation: 旭川市民文化会館（北海道・旭川市）
  • Year and Date: 2016-05-11
• [Presentation] マウスにおけるシリカナノ粒子の表面修飾と炎症誘導作用との関係 (2016)
  • Author(s): 渡邊 英里、ブラニッチ サンドラ、市原 佐保子、呉 文亭、鈴木 利宙、林田 有紗、長田 百合果、張 霊逸、ボーランド ソニア、トラン ラン、櫻井 敏博、安部 良、市原 学
  • Organizer: 第86回日本衛生学会学術総会
  • Place of Presentation: 旭川市民文化会館（北海道・旭川市）
  • Year and Date: 2016-05-11
• [Presentation] Effects of nano-sized TiO2 on the adhesion of monocytes to endothelial cells (2016)
  • Author(s): Sahoko Ichihara, Yuka Suzuki, Eri Watanabe, Yurika Osada, Arisa Hayashida, Tomoki Furutani, Kiyora Izioka, Gaku Ichihara
  • Organizer: The 55th Annual Meeting of Society of Toxicology and ToxExpo
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2016-03-13
  • Int'l Joint Research
• [Presentation] Nrf2欠損マウスにおけるカーボンナノチュブの影響とそ作用機序検討 (2016)
  • Author(s): 鈴木 悠加 、市原 学、呉 文亭、伊東 健、山本 雅之、出岡 淑、市原 佐保子
  • Organizer: 第15回分子予防環境医学研究会大会
  • Place of Presentation: 自治医科大学地域医療情報研修センター（栃木県、下野市）
  • Year and Date: 2016-01-29
• [Presentation] マウスにおけるシリカナノ粒子の表面修飾と炎症誘導作用との関係 (2015)
  • Author(s): 渡邊 英里, ブラニッチ サンドラ, 市原 佐保子, 呉 文亭, ボーラド ソニア, トラン ラン, 林田 有紗, 長田 百合果, 張 霊逸, 櫻井 敏博, 市原 学
  • Organizer: 第43 回産業中毒・生物学的モニタリング研究会
  • Place of Presentation: まるは食堂旅館（愛知県、知多郡）
  • Year and Date: 2015-10-02
• [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] Role of nuclear factor erythroid 2-related factor (Nrf2) in pulmonary inflammation induced by zinc oxide nanoparticles (2015)
  • Author(s): Radwa Sehsah, Wenting Wu, Sahoko Ichihara, Naozumi Hashimono, Yoshinori Hasegawa, A. El-Sayed, N. Joseph, S. El-Bestar, Emily Kamel, Gaku Ichihara
  • Organizer: Society of Occupational Medicine Annual Scientific Meeting
  • Place of Presentation: Manchester, UK
  • Year and Date: 2015-07-06
  • Int'l Joint Research
• [Presentation] シリカナノ粒子の表面修飾はマウス肺炎症反応に影響を与える (2015)
  • Author(s): Sandra Vranic, 市原 佐保子, 呉 文亭, 渡邊 英里, 櫻井 敏博, Sonja Boland, Lang Tran, 市原 学
  • Organizer: 第42回日本毒性学会学術年会
  • Place of Presentation: 石川県立音楽堂（石川県、金沢市）
  • Year and Date: 2015-06-29
• [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
  • 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
  • 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