Control of multiwall carbon nanotube-induced inflammatory responses by cellular cholesterol

• Project/Area Number: 23590164
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental pharmacy
• Research Institution: National Institute of Health Sciences
• Principal Investigator: NISHIMAKI-MOGAMI Tomoko 国立医薬品食品衛生研究所, 代謝生化学部, 部長 (90174333)
• Co-Investigator(Kenkyū-buntansha): OKUHIRA Keiichiro 国立医薬品食品衛生研究所, 機能生化学部, 室長 (10425671)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ナノ材料 / カーボンナノチューブ / コレステロール / インフラマソーム / IL-1β / NLRP3 / IL-1beta

Research Abstract

Because cnanotubes have asbestos-like shape and size, concerns about their adverse effect on environment and health have been raised. Studies have shown their association with inflammation, mesothelioma, and atherosclerosis progression in mice. In this study, we investigated the mechanism by which multiwall carbon nanotubes (MWCNT)-induced production of an inflammatory cytokine IL-1beta is regulated by cholesterol. We found that MWCNTs were incorporated into THP-1 macrophages and induced IL-1beta maturation via NLRP3 inflammasome activation. This effect is enhanced by dispersion of MWCNTs with lung-surfactant-like phospholipids. Various statins repressed MWCNT-induced IL-1beta release by reducing cellular uptake of MWCNTs.

Research Products

• [Journal Article] Hepatocyte Nuclear Factor 4alpha Increases Liver-specific Human ATP- Binding Cassette Transporter A1 Expression and Cholesterol Efflux to ApoA-I in Response to Cholesterol Depletion (2012)
  • Author(s): Ohoka N, Okuhira K, Cui H, Wu W, Sato R,Naito M, Nishimaki-Mogami T
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 32 Pages: 1005-1014
  • Peer Reviewed
• [Journal Article] Hepatocyte Nuclear Factor 4alpha Increases Liver-specific Human ATP-Binding Cassette Transporter A1 Expression and Cholesterol Efflux to ApoA-I in Response to Cholesterol Depletion. (2012)
  • Author(s): Ohoka N, Okuhira K, Cui H, Wu W, Sato R, Naito M, Nishimaki-Mogami T.
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 32 Pages: 1005-1014
  • Peer Reviewed
• [Presentation] High-temperature calcined fullerene nanowhiskers and multi-wall carbon nanotubes have abilities to induce IL-1beta secretion through NLRP3-dependent mechanism depending on their lengths (2013)
  • Author(s): Nishimaki-Mogami T, Cui H, Wu W, Okuhira K, Naito M, Nishimura T, Sakamoto Y, Ogata A, Maeno T, Inomata A, Nakae D, Miyazawa K, Hirose A
  • Organizer: Eurotox2013
  • Place of Presentation: Interlaken, Switzerland
  • Year and Date: 2013-09-03
• [Presentation] Hepatocyte Nuclear Factor 4alpha(HNF4alpha) Regulates Liver-specific Human ATP-binding Cassette Protein A1 (ABCA1) Gene Expression in Response to Cholesterol Depletion (2012)
  • Author(s): Ohoka N, Okuhira K, Cui H, Wu W, Naito M, Nishimaki-Mogami T
  • Organizer: ASBMB Symposium "Frontiers in Lipid Biology"
  • Place of Presentation: Banff, Canada
  • Year and Date: 2012-09-05
• [Presentation] Mechanism underlying multiwall carbon nanotube-induced IL-1beta secretion (2012)
  • Author(s): Nishimaki-Mogami T, Cui H, Okuhira K, Naito M, Suzuki K, Nishimura T, Hirose A
  • Organizer: EUROTOX 2012
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2012-06-19
• [Presentation] 多層カーボンナノチューブによるIL-1β産生促進とその機構 (2011)
  • Author(s): 最上(西巻)知子, 崔紅艶, 岩崎香里, 奥平桂一郎, 内藤幹彦, 鈴木和博, 広瀬明彦
  • Organizer: フォーラム2011衛生薬学・環境トキシコロジー
  • Place of Presentation: 金沢
  • Year and Date: 2011-10-28
• [Presentation] 多層カーボンナノチューブはNLRP3活性化を介してIL-1β産生を促進する (2011)
  • Author(s): 最上(西巻)知子, 崔紅艶, 岩崎香里, 奥平桂一郎, 内藤幹彦, 鈴木和博, 広瀬明彦
  • Organizer: 第38回日本トキシコロジー学会学術年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-07-11
• [Presentation] HDL産生トランスポーターABCA1のコレステロールによる肝型転写制御- (2011)
  • Author(s): 最上(西巻)知子
  • Organizer: ミニシンポジウム「脂質ホメオスタシス:その破綻と疾患」第12回Pharmaco-Hematologyシンポジウム
  • Place of Presentation: 富山
  • Year and Date: 2011-06-17
  • Invited
• [Presentation] 多層カーボンナノチューブによるIL-1β産生促進とその機構 (2011)
  • Author(s): 最上（西巻） 知子, 崔 紅艶, 岩崎 香里, 奥平 桂一郎, 内藤 幹彦, 鈴木 和博, 広瀬 明彦
  • Organizer: フォーラム2011 衛生薬学・環境トキシコロジー
  • Place of Presentation: 金沢
• [Presentation] HDL産生トランスポーターABCA1のコレステロールによる肝型転写制御 －ミニシンポジウム「脂質ホメオスタシス：その破綻と疾患」 (2011)
  • Author(s): 最上(西巻)知子
  • Organizer: 第12回Pharmaco-Hematologyシンポジウム(招待講演)
  • Place of Presentation: 富山
• [Presentation] High-temperature calcined fullerene nanowhiskers and multi-wall carbon nanotubes have abilities to induce IL-1beta secretion through NLRP3-dependent mechanism, depending on their lengths
  • Author(s): Nishimaki-Mogami T, Cui H, Wu W, Okuhira K, Naito M, Nishimura T, Sakamoto Y, Ogata A, Maeno T, Inomata A, Nakae D, Miyazawa K, Hirose A
  • Organizer: Eurotox2013
  • Place of Presentation: Interlaken, Switzerland
• [Presentation] Mechanism underlying multiwall carbon nanotube-induced IL-1beta secretion.
  • Author(s): Nishimaki-Mogami T, Cui H, Okuhira K, Naito M, Suzuki K, Nishimura T, Hirose A.
  • Organizer: EUROTOX 2012
  • Place of Presentation: Stockholm
• [Presentation] Hepatocyte Nuclear Factor 4alpha(HNF4alpha) Regulates Liver-specific Human ATP-binding Cassette Protein A1 (ABCA1) Gene Expression in Response to Cholesterol Depletion
  • Author(s): Ohoka N, Okuhira K, Cui H, Wu W, Naito M, Nishimaki-Mogami T.
  • Organizer: ASBMB Symposium "Frontiers in Lipid Biology"
  • Place of Presentation: Banff