Targeting cryopyrin as a new therapeutic approach to control inflammation

• Project/Area Number: 20591197
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Department of Clinical Research, National Hospital Organization Nagasaki Medical Center
• Principal Investigator: MIGITA Kiyoshi Department of Clinical Research, National Hospital Organization Nagasaki Medical Center, 臨床研究センター, 病因解析研究部長 (60264214)
• Co-Investigator(Kenkyū-buntansha): ISHIBASHI Hiromi 独立行政法人国立病院機構長崎医療センター, 臨床研究センター, センター長 (80127969) ; EGUCHI Katumi 長崎大学, 医歯薬学総合研究科, 教授 (30128160) ; 石橋 大海 独立行政法人国立病院機構(長崎医療センター臨床研究センター), 臨床研究センター長 (80127696)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ryopyrin / 自己炎症性疾患 / 家族性地中海熱 / 関節リウマチ / 血清アミロイドA蛋白 / Cryopyrin / cropyrin / MEFV遺伝子 / Pyrin / cryopyrin / pyrin / MEFV / アミロイドーシス

Research Abstract

The mechanism by which inflammasome activation and following IL-1β induction in autoinflammation is not completely elucidated. We studied the role of serum amyloid A (SAA) in the regulation of IL-1β production and activation of inflammasome cascade in human rheumatoid synoviocytes. Rheumatoid synoviocytes stimulated with SAA express NLRP3 (cryopyrin) mRAN expression. MSU (modosodium urate), a ligand for NLRP3, stimulation did not induce IL-1β production in rheumatoid synoviocytes. Whereas, rheumatoid synoviocytes pretreated with low concentration (1-5μg/ml) of SAA produce IL-1β in response to MSU. These findings indicate that during systemic inflammation, SAA may promote the MSU-induced IL-1β induction through activating the NLRP3 inflammasome activation.

Research Products

• [Journal Article] A Japanese case of familial Mediterranean fever presenting diffuse bone marrow uptake of FDG-PET and high levels of neutrophil membrane CD64 expression. (2011)
  • Author(s): Koga T, Umeda M, Migita K, Yamasaki S, Nakamura H, Kawakami A.
  • Journal Title: Rheumatology (Oxford). 50(6) Pages: 1171-3
  • Peer Reviewed
• [Journal Article] A Japanese case of familial Mediterranean fever presenting diffuse bone marrow uptake of FDG-PET and high levels of neutrophil membrane CD64 expression. (2011)
  • Author(s): Koga T, Umeda M, Migita K, Yamasaki S, Nakamura H, Kawakami A.
  • Journal Title: Rheumatology (Oxford). Volume: 50 Pages: 1171-1173
  • Peer Reviewed
• [Journal Article] Protracted synovitis without systemic manifestations in familial Mediterranean fever (FMF). (2010)
  • Author(s): Migita K, Torigoshi T, Motokawa S, Ito M, Miyashita T, Izumi Y, Yasunami M.
  • Journal Title: Clin Exp Rheumatol. 28(4 Suppl 60)
  • Peer Reviewed
• [Journal Article] 家族性地中海熱 (2010)
  • Author(s): 上松一永, 右田清志
  • Journal Title: 医学のあゆみ2010 235(12,13) Pages: 1159-1163
  • Peer Reviewed
• [Journal Article] Protracted synovitis without systemic manifestations in familial Mediterranean fever (FMF). (2010)
  • Author(s): Migita K, Torigoshi T, Motokawa S, Ito M, Miyashita T, Izumi Y, Yasunami M.
  • Journal Title: Clin Exp Rheumatol. Volume: 28
  • Peer Reviewed
• [Journal Article] 家族性地中海熱 (2010)
  • Author(s): 上松一永, 右田清志
  • Journal Title: 医学のあゆみ Volume: 235 Pages: 1159-1163
  • Peer Reviewed
• [Journal Article] Protracted synovitis without systemic manifestations in familial Mediter ranean fever(FMF). (2010)
  • Author(s): Migita,K, Torigoshi T, Jiuchi Y, Motokawa S, Ito M, Miyashita T, Koga T, Izumi Y, Yasunami M.
  • Journal Title: Chn Exp Rheumatol. (in press, 掲載確定)
  • Peer Reviewed
• [Journal Article] 自己炎症疾患-家族性地中海熱を中心に- (2009)
  • Author(s): 右田清志、古賀智裕、和泉泰衛、宮下賜一郎、石橋大海
  • Journal Title: 国立医療学会雑誌 医療 63 Pages: 363-369
  • NAID: 40016728209
• [Journal Article] 自己炎症疾患-家族性地中海熱の基礎と臨床- (2009)
  • Author(s): 右田清志
  • Journal Title: 九州リウマチ 29 Pages: 74-81
• [Journal Article] MEFV mutations in Japanese rheumatoid arthritis patients. (2008)
  • Author(s): Migita K, Nakamura T, Maeda Y, Miyashita T, Koga T, Tanaka M, Nakamura M, Komori A, Ishibashi H, Origuchi T, Ida H, Kawasaki E, Yasunami M, Eguchi K.
  • Journal Title: Clin Exp Rheumatol. 26(6) Pages: 1091-4
  • Peer Reviewed
• [Journal Article] MEFV mutations in Japanese rheumatoid arthritis patients (2008)
  • Author(s): Migita K, Nakamura T, Maeda Y, Miyashita T, Koga T, Tanaka M, Nakamura M, Komori A, Ishibashi H, Origuchi T, Ida H, Kawasaki E, Yasunami M, Eguchi K.
  • Journal Title: Clin Exp Rheumatol 26 Pages: 1091-4
  • Peer Reviewed
• [Remarks] ホームページ等