Neutrophils in inflammatory response induced by lipid crystals

• Project/Area Number: 18K08485
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Jichi 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: ¥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．

Research Products

• [Journal Article] Calciprotein Particles Induce IL-1β/α?Mediated Inflammation through NLRP3 Inflammasome-Dependent and -Independent Mechanisms (2021)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] GSDME-Dependent Incomplete Pyroptosis Permits Selective IL-1α Release under Caspase-1 Inhibition (2020)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] ASC regulates platelet activation and contributes to thrombus formation independent of NLRP3 inflammasome (2020)
  • 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
  • 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
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Cigarette smoke extract induces ferroptosis in vascular smooth muscle cells (2020)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Exogenous nanoparticles and endogenous crystalline molecules as danger signals for the?NLRP3 inflammasomes (2018)
  • 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
  • Peer Reviewed
• [Journal Article] Myeloid HMG-CoA (3-Hydroxy-3-Methylglutaryl-Coenzyme A) Reductase Determines Atherosclerosis by Modulating Migration of Macrophages (2018)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Inflammasome Activation Aggravates Cutaneous Xanthomatosis and Atherosclerosis in ACAT1 (Acyl-CoA Cholesterol Acyltransferase 1) Deficiency in Bone Marrow (2018)
  • 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
  • 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
  • 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
  • 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
  • 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
  • Invited
• [Presentation] Inflammatory crystal-mediated activation of NLRP3 inflammasome in the progression of atherosclerosis (2019)
  • Author(s): 唐澤 直義
  • Organizer: 第51回日本動脈硬化学会・学術集会
  • 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
• [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
• [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
  • Invited