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Neutrophils in inflammatory response induced by lipid crystals

Research Project

Project/Area Number 18K08485
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionJichi Medical University

Principal Investigator

Karasawa Tadayoshi  自治医科大学, 医学部, 講師 (60631893)

Co-Investigator(Kenkyū-buntansha) 高橋 将文  自治医科大学, 医学部, 教授 (40296108)
木村 博昭  自治医科大学, 医学部, 講師 (70593622)
渡邊 幸子  自治医科大学, 医学部, 助教 (80770619)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords好中球 / インフラマソーム / マクロファージ / コレステロール結晶 / カスパーゼ / 動脈硬化 / 細胞死 / Interleukin-1 / カスパーゼ1 / 飽和脂肪酸 / インターロイキン / 脂質結晶
Outline of Final Research Achievements

Cholesterol crystals deposited in atherosclerotic lesion activates NLRP3 inflammasome and induce inflammatory responses via interleukin-1. In this study, we investigated the involvement of IL-1 in cholesterol crystal-mediated neutrophil infiltration and found that IL-1α plays a pivotal role in this response. Our results indicate that IL-1α is an essential mediator in the inflammatory response induced by crystals and particles.

Academic Significance and Societal Importance of the Research Achievements

近年,心・血管病の予防における炎症性サイトカインIL-1βの重要性は臨床研究によっても示唆されている.本研究によりIL-1βだけでなく,IL-1αも重要な炎症の惹起因子であることが示されたことは,IL-1経路の阻害剤を治療に用いる上で,重要な知見になると期待される.

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (22 results)

All 2021 2020 2019 2018

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 12 results) Presentation (7 results) (of which Invited: 5 results)

  • [Journal Article] Calciprotein Particles Induce IL-1β/α?Mediated Inflammation through NLRP3 Inflammasome-Dependent and -Independent Mechanisms2021

    • Author(s)
      Anzai Fumiya、Karasawa Tadayoshi、Komada Takanori、Yamada Naoya、Miura Yutaka、Sampilvanjil Ariunaa、Baatarjav Chintogtokh、Fujimura Kenta、Matsumura Takayoshi、Tago Kenji、Kurosu Hiroshi、Takeishi Yasuchika、Kuro-O Makoto、Takahashi Masafumi
    • Journal Title

      ImmunoHorizons

      Volume: 5 Issue: 7 Pages: 602-614

    • DOI

      10.4049/immunohorizons.2100066

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GSDME-Dependent Incomplete Pyroptosis Permits Selective IL-1α Release under Caspase-1 Inhibition2020

    • Author(s)
      Aizawa Emi、Karasawa Tadayoshi、Watanabe Sachiko、Komada Takanori、Kimura Hiroaki、Kamata Ryo、Ito Homare、Hishida Erika、Yamada Naoya、Kasahara Tadashi、Mori Yoshiyuki、Takahashi Masafumi
    • Journal Title

      iScience

      Volume: 23 Issue: 5 Pages: 101070-101070

    • DOI

      10.1016/j.isci.2020.101070

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ASC regulates platelet activation and contributes to thrombus formation independent of NLRP3 inflammasome2020

    • Author(s)
      Watanabe Sachiko、Usui-Kawanishi Fumitake、Komada Takanori、Karasawa Tadayoshi、Kamata Ryo、Yamada Naoya、Kimura Hiroaki、Dezaki Katsuya、Ohmori Tsukasa、Takahashi Masafumi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 531 Issue: 2 Pages: 125-132

    • DOI

      10.1016/j.bbrc.2020.07.063

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Glucose regulates hypoxia-induced NLRP3 inflammasome activation in macrophages.2020

    • Author(s)
      1)Watanabe S, Usui-Kawanishi F, Karasawa, Kimura H, Kamata R, Inoue, Mise N, Kasahara T, Takahashi M
    • Journal Title

      J Cell Physiol

      Volume: - Issue: 10 Pages: 7554-7566

    • DOI

      10.1002/jcp.29659

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ferroptosis driven by radical oxidation of n-6 fatty acids mediates acetaminophen-induced acute liver failure.2020

    • Author(s)
      2)Yamada N, Karasawa T, Kimura H, Watanabe S, Komada T, Kamata R, Sampilvanjil A, Ito J, Nakagawa K, Kuwata H, Hara S, Sakuma Y, Sata N, Takahashi M
    • Journal Title

      Cell Death Dis

      Volume: 11 Issue: 2 Pages: 144-144

    • DOI

      10.1038/s41419-020-2334-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cigarette smoke extract induces ferroptosis in vascular smooth muscle cells2020

    • Author(s)
      Sampilvanjil Ariunaa、Karasawa Tadayoshi、Yamada Naoya、Komada Takanori、Higashi Tsunehito、Baatarjav Chintogtokh、Watanabe Sachiko、Kamata Ryo、Ohno Nobuhiko、Takahashi Masafumi
    • Journal Title

      American Journal of Physiology-Heart and Circulatory Physiology

      Volume: 318 Issue: 3 Pages: H508-H518

    • DOI

      10.1152/ajpheart.00559.2019

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Iron overload as a risk factor for hepatic ischemia-reperfusion injury in liver transplantation: potential role of ferroptosis.2020

    • Author(s)
      3)Yamada N, Karasawa T, Wakiya T, Sadatomo A, Ito H, Kamata R, Watanabe S, Komada T, Kimura H, Sanada Y, Sakuma Y, Mizuta K, Sata N, Takahashi M
    • Journal Title

      Am J Transplant

      Volume: - Issue: 6 Pages: 1606-1618

    • DOI

      10.1111/ajt.15773

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Crucial role of NLRP3 inflammasome in a murine model of Kawasaki disease.2020

    • Author(s)
      4)Anzai F, Watanabe S, Kimura H, Kamata R, Karasawa T, Komada T, Nakamura J, Nagi-Miura N, Ohno N, Takeishi Y, Takahashi M
    • Journal Title

      J Mol Cell Cardiol

      Volume: 138 Pages: 185-196

    • DOI

      10.1016/j.yjmcc.2019.11.158

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of TLR5 in inflammation and tissue damage after intestinal ischemia-reperfusion injury.2019

    • Author(s)
      7)Ito H, Sadatomo A, Inoue Y, Yamada N, Aizawa E, Hishida E, Kamata R, Karasawa T, Kimura H, Watanabe S, Komada T, Horie H, Kitagawa J, Sata N, Takahashi M
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 519 Issue: 1 Pages: 15-22

    • DOI

      10.1016/j.bbrc.2019.08.083

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Crucial role of NLRP3 inflammasome in the development of peritoneal dialysis-related peritoneal fibrosis.2019

    • Author(s)
      6)Hishida E, Ito H, Komada T, Karasawa T, Kimura H, Watanabe S, Kamata R, Aizawa E, Kasahara T, Morishita Y, AkimotoT, Nagata D, Takahashi M
    • Journal Title

      Sci Rep

      Volume: 9 Issue: 1 Pages: 10363-10363

    • DOI

      10.1038/s41598-019-46504-1

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inflammasome-independent and atypical processing of IL-1β contributes to acid aspiration-induced acute lung injury.2019

    • Author(s)
      5)Mizushina Y, Karasawa T, Aizawa K, Kimura H, Watanabe S, Kamata R, Komada T, Mato N, Kasahara T, Koyama S, Bando M, Hagiwara K, Takahashi M
    • Journal Title

      J Immunol

      Volume: 203 Issue: 1 Pages: 236-246

    • DOI

      10.4049/jimmunol.1900168

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exogenous nanoparticles and endogenous crystalline molecules as danger signals for the?NLRP3 inflammasomes2018

    • Author(s)
      Shirasuna Koumei、Karasawa Tadayoshi、Takahashi Masafumi
    • Journal Title

      Journal of Cellular Physiology

      Volume: 234 Issue: 5 Pages: 5436-5450

    • DOI

      10.1002/jcp.27475

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Myeloid HMG-CoA (3-Hydroxy-3-Methylglutaryl-Coenzyme A) Reductase Determines Atherosclerosis by Modulating Migration of Macrophages2018

    • Author(s)
      Sakai Kent、Nagashima Shuichi、Wakabayashi Tetsuji、Tumenbayar Bayasgalan、Hayakawa Hiroko、Hayakawa Morisada、Karasawa Tadayoshi、Ohashi Ken、Yamazaki Hisataka、Takei Akihito、Takei Shoko、Yamamuro Daisuke、Takahashi Manabu、Yagyu Hiroaki、Osuga Jun-ichi、Takahashi Masafumi、Tominaga Shin-ichi、Ishibashi Shun
    • Journal Title

      Arteriosclerosis, Thrombosis, and Vascular Biology

      Volume: 38 Issue: 11 Pages: 2590-2600

    • DOI

      10.1161/atvbaha.118.311664

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inflammasome Activation Aggravates Cutaneous Xanthomatosis and Atherosclerosis in ACAT1 (Acyl-CoA Cholesterol Acyltransferase 1) Deficiency in Bone Marrow2018

    • Author(s)
      Wakabayashi Tetsuji、Takahashi Manabu、Yamamuro Daisuke、Karasawa Tadayoshi、Takei Akihito、Takei Shoko、Yamazaki Hisataka、Nagashima Shuichi、Ebihara Ken、Takahashi Masafumi、Ishibashi Shun
    • Journal Title

      Arteriosclerosis, Thrombosis, and Vascular Biology

      Volume: 38 Issue: 11 Pages: 2576-2589

    • DOI

      10.1161/atvbaha.118.311648

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adeno-associated Virus Vector-mediated Interleukin-10 Induction Prevents Vascular Inflammation in a Murine Model of Kawasaki Disease.2018

    • Author(s)
      Nakamura J, Watanabe S, Kimura H, Kobayashi M, Karasawa T, Kamata R, Usui-Kawanishi F, Sadatomo A, Mizukami H, Nagi-Miura N, Ohno N, Kasahara T, Minota S, Takahashi M.
    • Journal Title

      Sci Rep

      Volume: 8 Issue: 1 Pages: 7601-7601

    • DOI

      10.1038/s41598-018-25856-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 脂肪酸によるNLRP3インフラマソームを介した炎症惹起機構と動脈硬化2021

    • Author(s)
      唐澤 直義
    • Organizer
      第53回日本動脈硬化学会総会・学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 心血管病におけるインフラマソームの役割2019

    • Author(s)
      唐澤 直義, 高橋 将文
    • Organizer
      脳心血管抗加齢研究会2019
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 動脈硬化の進展におけるNLRP3インフラマソームの役割2019

    • Author(s)
      唐澤 直義,高橋 将文
    • Organizer
      第40回 日本炎症・再生医学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Inflammatory crystal-mediated activation of NLRP3 inflammasome in the progression of atherosclerosis2019

    • Author(s)
      唐澤 直義
    • Organizer
      第51回日本動脈硬化学会・学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 飽和脂肪酸は結晶形成を介して好中球浸潤を引き起こす2019

    • Author(s)
      唐澤 直義,駒田敬則, 高橋 将文
    • Organizer
      脳心血管抗加齢研究会2019
    • Related Report
      2019 Research-status Report
  • [Presentation] 飽和脂肪酸の結晶形成を介した炎症惹起機構の解明2018

    • Author(s)
      唐澤 直義, 渡邊 幸子, 木村 博昭, 松坂 賢, 島野 仁, 高橋 将文
    • Organizer
      第55回 日本臨床分子医学会 学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] コレステロール結晶の炎症惹起のメカニズム2018

    • Author(s)
      唐澤 直義
    • Organizer
      12th Trans Catheter Imaging Forum
    • Related Report
      2018 Research-status Report
    • Invited

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Published: 2018-04-23   Modified: 2023-01-30  

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