Elucidation of novel regulatory mechanisms of inflammasome in metabolic disease

• Project/Area Number: 24890217
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Metabolomics
• Research Institution: Jichi Medical University
• Principal Investigator: KARASAWA Tadayoshi 自治医科大学, 医学部, 助教 (60631893)
• Project Period (FY): 2012-08-31 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 炎症 / インフラマソーム / インターロイキン / 脂肪酸 / カスパーゼ1 / マクロファージ / 自然免疫 / 慢性炎症 / 動脈硬化 / インスリン抵抗性

Outline of Final Research Achievements

Increasing evidences indicate that inflammation is involved in various aspects of metabolic disease. In this process, inflammasome plays critical role to initiate inflammatory response by activation of caspase-1. To investigate the novel regulatory mechanisms of inflammasome, I examined the role of CARD-only proteins (COPs) which are known as homologs of caspase-1. I identified that CARD16 exhibits higher expression levels than other COPs in human peripheral blood mononuclear cells. Furthermore, functional analysis in transfected HeLa cells revealed that oligomerization activity allows CARD16 to function as a caspase-1 activator. These results suggest CARD16 might promote inflammatory response by activation of caspase-1 and subsequent interleukin-1 β release.

Research Products

• [Journal Article] Oligomerized CARD16 Promotes Caspase-1 Assembly and IL-1β Processing (2015)
  • Author(s): Tadayoshi Karasawa, Akira Kawashima, Fumitake Usui, Hiroaki Kimura, Koumei Shirasuna, Yoshiyuki Inoue, Takanori Komada, Motoi Kobayashi, Yoshiko Mizushina, Junji Sagara, Masafumi Takahashi
  • Journal Title: FEBS Open Bio Volume: 5 Issue: 1 Pages: 348-356
  • DOI: 10.1016/j.fob.2015.04.011
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Critical role of caspase-1 in vascular inflammation and development of atherosclerosis in Western diet-fed apolipoprotein E-deficient mice. (2012)
  • Author(s): Usui F, Shirasuna K, Kimura H, Tatsumi K, Kawashima A, Karasawa T, Hida S, Sagara J, Taniguchi S, Takahashi M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 425 Issue: 2 Pages: 162-168
  • DOI: 10.1016/j.bbrc.2012.07.058
  • Peer Reviewed
• [Presentation] カスパーゼ１ホモログCOPs による炎症制御機構の解析 (2014)
  • Author(s): 唐澤 直義， 川島 晃， 臼井 文武， 木村 博昭， 高橋 将文
  • Organizer: 第46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: 2014-07-11
• [Presentation] カスパーゼ１ホモログ分子CARD16 による新規炎症惹起機序の解析 (2014)
  • Author(s): 唐澤 直義， 川島 晃， 臼井 文武， 木村 博昭， 高橋 将文
  • Organizer: 第35回日本炎症・再生医学会
  • Place of Presentation: 万国津梁館（沖縄）
  • Year and Date: 2014-07-01