Elucidation of pathogenesis of drug-induced immune diseases caused by activation of inflammasome

• Project/Area Number: 16K15146
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Tohoku University
• Principal Investigator: Matsuzawa Atsushi 東北大学, 薬学研究科, 教授 (80345256)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 薬剤誘発性免疫疾患 / インフラマソーム / 炎症性サイトカイン / NLRPファミリー分子 / 薬剤副作用

Outline of Final Research Achievements

Drug-induced immune diseases, such as interstitial pneumonia caused by the anticancer drug Gefitinib, are considered to be fatal and severe side effects and important problems, which must be solved in the field of pharmaceutical health science. However, the actual cause of the diseases is not yet well understood. Inflammasomes, intracellular receptors recognizing pathogens and foreign materials, induce inflammation and cell death and have recently been shown to be the cause of various immune diseases. In this study, we revealed that several drugs activate inflammasomes composed of NLRP family molecules, and that drug-induced immune diseases may be partially caused by abnormal promotion of immune response through the activation of inflammasomes.

Research Products

• [Journal Article] ASK1キナーゼによるレドックスシグナル制御－多彩な翻訳後修飾を介したシグナル制御とその破綻による疾患 (2018)
  • Author(s): 松沢厚，一條秀憲
  • Journal Title: 実験医学 増刊「レドックス疾患学」 Volume: 36 Pages: 692-698
• [Journal Article] TRIM48 promotes ASK1 activation and cell death through ubiquitination-dependent degradation of the ASK1 negative regulator PRMT1. (2017)
  • Author(s): Hirata, Y., Katagiri, K., Nagaoka, K., Morishita, T., Kudoh, Y., Hatta, T., Naguro, I., Kano, K., Udagawa, T., Natsume, T., Aoki, J., Inada, T., Noguchi, T., Ichijo, H., Matsuzawa, A.
  • Journal Title: Cell Rep. Volume: 21 Issue: 9 Pages: 2447-2457
  • DOI: 10.1016/j.celrep.2017.11.007
  • Peer Reviewed / Open Access
• [Journal Article] Trans-fatty acids promote proinflammatory signaling and cell death by stimulating the apoptosis signal-regulating kinase 1 (ASK1)-p38 pathway. (2017)
  • Author(s): Hirata, Y., Takahashi, M., Kudoh, Y., Kano, K., Kawana, H., Makide, K., Shinoda, Y., Yabuki, Y., Fukunaga, K., Aoki, J., Noguchi, T., Matsuzawa, A.
  • Journal Title: J. Biol. Chem. Volume: 印刷中 Issue: 20 Pages: 8174-8185
  • DOI: 10.1074/jbc.m116.771519
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Activation of nuclear receptor CAR by an environmental pollutant perfluorooctanoic acid. (2017)
  • Author(s): Abe, T., Takahashi, M., Kano, M., Amaike, Y., Ishii, C., Maeda, K., Kudoh, Y., Morishita, T., Hosaka, T., Sasaki, T., Kodama, S., Matsuzawa, A., Kojima, H., Yoshinari, K.
  • Journal Title: Arch. Toxicol. Volume: 印刷中 Issue: 6 Pages: 2365-2374
  • DOI: 10.1007/s00204-016-1888-3
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Physiological roles of ASK family members in innate immunity and their involvement in pathogenesis of immune diseases. (2017)
  • Author(s): Matsuzawa, A.
  • Journal Title: Adv. Biol. Regul. Volume: 66 Pages: 46-53
  • DOI: 10.1016/j.jbior.2017.10.007
  • Peer Reviewed
• [Journal Article] Post-Translational Modifications of the TAK1-TAB Complex. (2017)
  • Author(s): Hirata, Y., Takahashi, M., Morishita, T., Noguchi, T., Matsuzawa, A.
  • Journal Title: Int. J. Mol. Sci. Volume: 18 Issue: 1 Pages: 205-205
  • DOI: 10.3390/ijms18010205
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Thioredoxin and redox signaling: Roles of the thioredoxin system in control of cell fate. (2017)
  • Author(s): Matsuzawa, A.
  • Journal Title: Arch. Biochem. Biophys. Volume: 617 Pages: 101-105
  • DOI: 10.1016/j.abb.2016.09.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Brefeldin A-inhibited guanine nucleotide-exchange factor 1 (BIG1) governs the recruitment of tumor necrosis factor receptor-associated factor 2 (TRAF2) to tumor necrosis factor receptor 1 (TNFR1) signaling complexes. (2016)
  • Author(s): Noguchi, T., Tsuchida, M., Kogue, Y., Spadini, C., Hirata, Y., Matsuzawa, A.
  • Journal Title: Int. J. Mol. Sci. Volume: 17 Issue: 11 Pages: 1869-1869
  • DOI: 10.3390/ijms17111869
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] キナーゼシグナルを厳密に制御する多様なユビキチン化関連酵素群の生理機能 (2016)
  • Author(s): 松沢厚
  • Journal Title: 日本応用酵素協会誌 Volume: 51 Pages: 7-15
• [Presentation] セファロスポリン系抗菌薬による細胞障害誘導機構 (2017)
  • Author(s): 宮川紗央子，武藤夏美，平田祐介，野口拓也，松沢厚
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-24
• [Presentation] Signaling mechanisms sensing and responding to various types of stress (2017)
  • Author(s): Atsushi Matsuzawa
  • Organizer: The 14th International Conference on Flow Dynamics, “Advanced Physical Stimuli and Biological Responses (Symposium)”
  • Int'l Joint Research / Invited
• [Presentation] ストレス応答シグナルの多様な翻訳後修飾を介した新たな制御機構 (2017)
  • Author(s): 松沢厚
  • Organizer: 第44回日本毒性学会学術年会
  • Invited
• [Presentation] Novel mechanisms of ALIS-mediated cellular dysfunction and death caused by antibacterial cephalosporins (2017)
  • Author(s): Midori Suzuki, Natsumi Mutoh, Sayoko Miyagawa, Yusuke Hirata, Takuya Noguchi, Atsushi Matsuzawa
  • Organizer: The 12th International Conference and 5th Asian Congress on Environmental Mutagens (ICEM-ACEM 2017)
  • Int'l Joint Research
• [Presentation] セファロスポリン系抗菌薬による細胞内凝集体ALISを介した新たな細胞障害・細胞死誘導機構 (2017)
  • Author(s): 武藤夏美，鈴木碧，宮川紗央子，平田祐介，野口拓也，松沢厚
  • Organizer: 第56回日本薬学会東北支部大会
• [Presentation] 分子標的薬ゲフィチニブが誘導する新たな細胞障害亢進機構 (2017)
  • Author(s): 関口雄斗，土田芽衣，平田祐介，野口拓也，松沢厚
  • Organizer: フォーラム2017衛生薬学・環境トキシコロジー
• [Presentation] セファロスポリン系抗菌薬による細胞内擬集体ALISを介した新たな細胞障害・細胞死誘導機構 (2017)
  • Author(s): 武藤夏美，鈴木碧，宮川紗央子，平田祐介，野口拓也，松沢厚
  • Organizer: フォーラム2017衛生薬学・環境トキシコロジー
• [Presentation] セファロスポリン系抗菌薬による細胞障害誘導機構 (2017)
  • Author(s): 鈴木碧，武藤夏美，平田祐介，野口拓也，松沢厚
  • Organizer: 第44回日本毒性学会学術年会
• [Presentation] ゲフィチニブによる新規細胞毒性作用の分子機構 (2017)
  • Author(s): 土田芽衣，関口雄斗，工藤勇気，平田祐介，野口拓也，松沢厚
  • Organizer: 第44回日本毒性学会学術年会
• [Presentation] バンコマイシンによるIL-1β分泌機構の解析 (2017)
  • Author(s): 野口拓也，工藤勇気，鈴木碧，西舘亜紀子，平田祐介，松沢厚
  • Organizer: 第44回日本毒性学会学術年会
• [Presentation] バンコマイシンによるIL-1β分泌機構の解析 (2016)
  • Author(s): 野口拓也，西舘亜紀子，松井稜祐，平田祐介，松沢厚
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
• [Presentation] バンコマイシンによるIL-1β分泌機構の解析 (2016)
  • Author(s): 松井稜祐，西舘亜紀子，平田祐介，野口拓也，松沢厚
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-25
• [Presentation] セファロスポリン系抗菌薬による酸化ストレス依存的な細胞障害機構 (2016)
  • Author(s): 武藤夏美，平田祐介，野口拓也，松沢厚
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-25
• [Presentation] ストレス応答シグナルのユビキチン化関連酵素群による新たな調節機構 (2016)
  • Author(s): 松沢厚
  • Organizer: フォーラム2016 衛生薬学・環境トキシコロジー
  • Place of Presentation: 東京
  • Year and Date: 2016-09-10
  • Invited
• [Presentation] Trans-fatty acids promote extracellular ATP-induced apoptosis through enhancing ROS-dependent activation of p38 MAP kinase (2016)
  • Author(s): Yusuke Hirata, Miki Takahashi, Yuki Kudoh, Takuya Noguchi, Atsushi Matsuzawa
  • Organizer: Forum 2016 Pharmaceutical Health Science, Environmental Toxicology
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2016-09-10
  • Int'l Joint Research
• [Presentation] セファロスポリン系抗菌薬による酸化ストレス依存的な細胞障害機構 (2016)
  • Author(s): 野口拓也，武藤夏美，平田祐介，松沢厚
  • Organizer: フォーラム2016 衛生薬学・環境トキシコロジー
  • Place of Presentation: 東京
  • Year and Date: 2016-09-10
• [Presentation] バンコマイシンによるIL-1β分泌機構の解析 (2016)
  • Author(s): 西舘亜紀子，平田祐介，野口拓也，松沢厚
  • Organizer: フォーラム2016 衛生薬学・環境トキシコロジー
  • Place of Presentation: 東京
  • Year and Date: 2016-09-10
• [Presentation] 多様なストレス感知-応答制御の仕組み －衛生薬学の視点からのストレス応答シグナル研 究の展開－ (2016)
  • Author(s): 松沢厚
  • Organizer: 第3回衛生薬学・環境トキシコロジー 若手研究者の会 シンポ ジウム
  • Place of Presentation: 東京
  • Year and Date: 2016-09-09
  • Invited
• [Book] 衛生薬学 健康と環境 (第6版)，永沼章・姫野誠一郎・平塚明 編 (2018)
  • Author(s): 松沢厚
  • Total Pages: 538
  • Publisher: 丸善出版
  • ISBN: 9784621301784
• [Remarks] 東北大学 大学院薬学研究科 衛生化学分野
  • URL: http://www.pharm.tohoku.ac.jp/~eisei/eisei.HP/index.html