Molecular mechanism of cell death induced by the activation of intracellular pattern recognition receptor, cryopyrin

• Project/Area Number: 19591303
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Chiba University
• Principal Investigator: KAMBE Naotomo Chiba University, 大学院・医学研究院, 講師 (50335254)
• Co-Investigator(Kenkyū-buntansha): NISHIKOMORI Ryuta 京都大学, 大学院・医学研究科, 助教 (70359800)
• Co-Investigator(Renkei-kenkyūsha): NISHIKOMORI Ryuta 京都大学, 大学院・医学研究科, 助教 (70359800)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 皮膚感染症 / 免疫学 / NLRP3 / CIAS1 / cryopyrin / 細胞内パターン認識受容体 / 細胞死 / ASC / cathepsin B / 細胞内微生物認識受容体 / catyepsinB / TAPtag法

Research Abstract

NLRP3の活性化によってネクローシス様の細胞死が起こる機序を明らかにするため、NLRP3のPYDドメイン,下流分子であるASCの全長およびそのCARDあるいはPYDドメインを,GFPとFKBPとのキメラ蛋白質としてウイルスベクターにクローニングした。CAPSにおいて肥満細胞がIL-1βを産生することを同定した上で,肥満細胞株MC/9に導入し,FKBPを介して特徴的な細胞死を誘導できる系を樹立した。この結果,細胞死が誘導された際にどのような分子が関わっているのかを検討することが可能となった。

Research Products

• [Journal Article] Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria (2009)
  • Author(s): Nakamura Y, Kambe N, Saito M, Nishikomori R, Kim YG, Murakami M, Nunez G, Matsue H.
  • Journal Title: J Exp Med (in press)
  • Peer Reviewed
• [Journal Article] Role of the NOD2 genotype in the clinical phenotype of Blau syndrome and early-onset sarcoidosis (2009)
  • Author(s): Okafuji I, Nishikomori R, Kanazawa N, Kambe N, Fujisawa A, Yamazaki S, Saito M, Yoshioka T, Kawai T, Sakai H, Tanizaki H, Heike T, Miyachi Y, Nakahata T.
  • Journal Title: Arthritis Rheum 60 Pages: 242-250
  • Peer Reviewed
• [Journal Article] Role of the NOD2 genotype in the clinical phenotype of Blau syndrome and early-onset sarcoidosis (2009)
  • Author(s): Okafuji I, anishikomori R, Kanazawa N, Kambe N, et al.
  • Journal Title: Arthritis Rheum 60 Pages: 242-250
  • Peer Reviewed
• [Journal Article] Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria (2009)
  • Author(s): Nakamura Y, Kambe N, et al.
  • Journal Title: J Exp med (in press)
  • Peer Reviewed
• [Journal Article] Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients (2008)
  • Author(s): Saito M, Nishikomori R, Kambe N, Fujisawa A, Tanizaki H, Takeichi K, Imagawa T, Iehara T, Takada H, Matsubayashi T, Tanaka H, Kawashima H, Kawakami K, Kagami S, Okafuji I, Yoshioka T, Adachi S, Heike T, Miyachi Y, Nakahata T.
  • Journal Title: Blood 111 Pages: 2132-41
  • Peer Reviewed
• [Journal Article] Disease-associated CIAS1 mutations induce monocyte death,revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients (2008)
  • Author(s): Saito M, Nishikomori R, Kambe N, et. al.
  • Journal Title: Blood 111 Pages: 2132-41
  • Peer Reviewed
• [Journal Article] Disease-associated mutations in CIAS1 induce cathepsin B-dependent rapid cell death of human THP-1 monocytic cells (2007)
  • Author(s): Fujisawa A, Kambe N, Saito M, Nishikomori R, Tanizaki H, Kanazawa N, Adachi S, Heike T, Sagara J, Suda T, Nakahata T, Miyachi Y.
  • Journal Title: Blood 109 Pages: 2903-11
  • Peer Reviewed
• [Journal Article] Disease-associated mutations in CIAS1 induce cathepsin B-dependent rapid cell death of human THP-1 monocytic cells (2007)
  • Author(s): Fujisawa A, Kambe N, et. al.
  • Journal Title: Blood 109 Pages: 2903-11
  • Peer Reviewed
• [Presentation] NLRP3-inflammasomeを介したIL-1β産生とヒスタミン非依存性蕁麻疹 (2009)
  • Author(s): 神戸直智
  • Organizer: 第18回東京免疫フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2009-03-12
• [Presentation] 自己炎症性疾患において肥満細はNLRP3 inflammasomeを介して好中球遊走と血管透過性を制御する (2008)
  • Author(s): 中村悠美, 神戸直智, 松江弘之
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
• [Presentation] NLRP3の活性化によって誘導されるpyronecrosisの分子学的機序 (2008)
  • Author(s): 佐藤貴史, 中村悠美, 神戸直智, 松江弘之
  • Organizer: 第15回分子皮膚科学フォーラム
  • Place of Presentation: 京都
• [Presentation] 肥満細胞に発現するNLRP3インフラマソームを介したIL-1βの産生は生体内で好中球主体の炎症と血管透過性の亢進を誘導する (2008)
  • Author(s): 中村悠美, 神戸直智, 松江弘之
  • Organizer: 第15回分子皮膚科学フォーラム
  • Place of Presentation: 京都
• [Presentation] Cryopyrin-associated IL-1 beta secretion inmast cells and a role played by mast cells in autoinflammatory disorders (2008)
  • Author(s): Nakamura Y, Kambe N, Matsue H.
  • Organizer: International Investigative Dermatology
  • Place of Presentation: Kyoto, Japan
• [Presentation] A case of early-onset sarcoidosis who showed spontaneous regression of his clinical manifestations but inherited skin eruption to his baby : What should we call this systemic inflammatory granulomatosis associated with NOD2 mutation (2008)
  • Author(s): Kambe N, Nakamura Y, Okafuji I, Nishikomori R, Kanazawa N, Matsue H.
  • Organizer: V International Congress on Familial Mediterranean Fever and Systemic Autoinflammatory Diseases
  • Place of Presentation: Rome, Itary
• [Presentation] Cryopyrin-associated IL-1 beta secretion in mast cells and a role played by mast cells in autoinflammatory disorders. (2008)
  • Author(s): Nakamura Y, Kambe N, et al.
  • Organizer: International Investigative Dermatology 2008
  • Place of Presentation: Kyoto, Japan