The role of inflammasome in prolonged inflammation of atherosclerosis

• Project/Area Number: 16K19544
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Jichi Medical University
• Principal Investigator: Tadayoshi Karasawa 自治医科大学, 医学部, 助教 (60631893)
• Project Period (FY): 2016-04-01 – 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 動脈硬化 / マクロファージ / 炎症 / 細胞死 / サイトカイン / カスパーゼ-1 / インフラマソーム / 慢性炎症

Outline of Final Research Achievements

NLRP3 inflammasome is a multiple cytoplasmic protein complex which is involved in innate immune response. In response to various DAMPs such as cholesterol crystals and saturated fatty acids, NLRP3 inflammasome regulates caspase-1 activation and subsequent IL-1beta processing. In this study, we aimed to clarify the role of NLRP3 inflammasome in prolonged inflammation of atherosclerosis. In order to investigate this issue, we developed inducible caspase-1 knockout mice using Cre-loxP system in an apoe-deficient background. The developed model is expected to be a useful tool to analyze the mechanisms of prolonged inflammation of atherosclerosis.

Research Products

• [Journal Article] Saturated Fatty Acids Undergo Intracellular Crystallization and Activate the NLRP3 Inflammasome in MacrophagesHighlights (2018)
  • Author(s): Karasawa Tadayoshi、Kawashima Akira、Usui-Kawanishi Fumitake、Watanabe Sachiko、Kimura Hiroaki、Kamata Ryo、Shirasuna Koumei、Koyama Yutaro、Sato-Tomita Ayana、Matsuzaka Takashi、Tomoda Hiroshi、Park Sam-Yong、Shibayama Naoya、Shimano Hitoshi、Kasahara Tadashi、Takahashi Masafumi
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology Volume: 38 Issue: 4 Pages: 744-756
  • DOI: 10.1161/atvbaha.117.310581
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The crystal-induced activation of NLRP3 inflammasomes in atherosclerosis. (2017)
  • Author(s): Karasawa T, Takahashi M.
  • Journal Title: Inflammation and Regeneration Volume: 37 Issue: 1 Pages: 18-18
  • DOI: 10.1186/s41232-017-0050-9
  • Peer Reviewed / Open Access
• [Journal Article] ARIH2 ubiquitinates NLRP3 and negatively regulates NLRP3 inflammasome activation in macrophages (2017)
  • Author(s): Kawashima Akira、Karasawa Tadayoshi、Tago Kenji、Kimura Hiroaki、Kamata Ryo、Usui-Kawanishi Fumitake、Watanabe Sachiko、Ohta Satoshi、Funakoshi-Tago Megumi、Yanagisawa Ken、Kasahara Tadashi、Suzuki Koichi、Takahashi Masafumi
  • Journal Title: The Journal of Immunology Volume: 199 Issue: 10 Pages: 3614
  • DOI: 10.4049/jimmunol.1700184
  • Peer Reviewed / Open Access
• [Journal Article] Interaction of Neutrophils with Macrophages Promotes IL-1β Maturation and Contributes to Hepatic Ischemia?Reperfusion Injury (2017)
  • Author(s): Sadatomo Ai、Inoue Yoshiyuki、Ito Homare、Karasawa Tadayoshi、Kimura Hiroaki、Watanabe Sachiko、Mizushina Yoshiko、Nakamura Jun、Kamata Ryo、Kasahara Tadashi、Horie Hisanaga、Sata Naohiro、Takahashi Masafumi
  • Journal Title: The Journal of Immunology Volume: 199 Issue: 9 Pages: 3306-3315
  • DOI: 10.4049/jimmunol.1700717
  • Peer Reviewed
• [Journal Article] The cardiac glycoside ouabain activates NLRP3 inflammasomes and promotes cardiac inflammation and dysfunction (2017)
  • Author(s): Kobayashi Motoi、Usui-Kawanishi Fumitake、Karasawa Tadayoshi、Kimura Hiroaki、Watanabe Sachiko、Mise Nathan、Kayama Fujio、Kasahara Tadashi、Hasebe Naoyuki、Takahashi Masafumi
  • Journal Title: PLOS ONE Volume: 12 Issue: 5 Pages: 176676-176676
  • DOI: 10.1371/journal.pone.0176676
  • Peer Reviewed / Open Access
• [Journal Article] Role of NLRP3 Inflammasomes in Atherosclerosis (2017)
  • Author(s): Karasawa, T.,Takahashi, M
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 24 Issue: 5 Pages: 443-451
  • DOI: 10.5551/jat.RV17001
  • NAID: 130005631688
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed
• [Journal Article] Caspse-1 deficiency promotes high-fat diet-induced adipose tissue inflammation and the development of obesity. (2016)
  • Author(s): Kimura H, Karasawa T, Usui F, Kawashima A, Endo Y, Kobayashi M, Sadatomo A, Nakamura J, Iwasaki Y, T Yada,Tsutsui H, Kasahara T, Takahashi M.
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 311 Issue: 5 Pages: 881-890
  • DOI: 10.1152/ajpendo.00174.2016
  • Peer Reviewed
• [Journal Article] NLRP3 reduces macrophage interleukin-10 production and enhances the susceptibility to doxorubicin-induced cardiotoxicity. (2016)
  • Author(s): Kobayashi M, Usui F, Karasawa T, Kawashima A, Kimura H, Mizushina Y, Shirasuna K, Mizukami H, Kasahara T, Hasebe N, Takahashi M.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 26489-26489
  • DOI: 10.1038/srep26489
  • Peer Reviewed / Open Access
• [Presentation] 飽和脂肪酸は結晶形成を介して好中球浸潤を誘導する (2017)
  • Author(s): 唐澤 直義, 渡邊 幸子, 木村 博昭, 高橋 将文
  • Organizer: 第38回日本炎症・再生医学会
• [Presentation] 飽和脂肪酸によるインフラマソーム活性化機構の解析 (2016)
  • Author(s): 唐澤 直義, 臼井 文武, 川島 晃, 木村 博昭, 高橋 将文
  • Organizer: 第48回日本動脈硬化学会 学術集会
  • Place of Presentation: 京王プラザホテル（東京）
  • Year and Date: 2016-07-15
• [Presentation] 脂肪酸結晶によるNLRP3インフラマソームを介した炎症惹起機構の解析 (2016)
  • Author(s): 唐澤 直義, 臼井 文武, 川島 晃, 木村 博昭, 高橋 将文
  • Organizer: 第37回日本炎症・再生医学会
  • Place of Presentation: 京都市勧業館みやこめっせ（京都）
  • Year and Date: 2016-06-16