プロテアソーム活性低下に起因する自己炎症病態の解明

2014 Fiscal Year Research-status Report

• Project/Area Number: 25461478
• Research Institution: Nagasaki University
• Principal Investigator: 有馬 和彦 長崎大学, 医歯薬学総合研究科(医学系), 講師 (30423635)
• Co-Investigator(Kenkyū-buntansha): 井田 弘明 久留米大学, 医学部, 教授 (60363496)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 慢性炎症 / 炎症性疾患

Outline of Annual Research Achievements

中條―西村症候群は、本邦にしか報告のない原因不明の遺伝性炎症性疾患である。近年我々はプロテアソームサブユニットの疾患特異的変異とその活性低下を見いだした。本症候群は世界で初めてのヒトにおけるプロテアソーム機能不全症である。　プロテアソーム活性低下に起因する炎症関連分子増加機構を分析し、他の炎症性疾患病態への関与を検証する。初めての機能不全症から解明される新規自己炎症病態を理解することは、他の炎症性疾患の病態理解を深めるとともに、新しい治療表的分子の同定と病勢判定検査の開発に貢献できる。本研究は炎症制御戦略の新展開に繋がると期待される。
培養細胞をプロテアソーム阻害剤(MG-132, Lactacystin, Epoxomicin, MG-115, MG-262)存在下に培養を行い、培養可能な細胞死を起こさない薬剤濃度を得た。血清刺激を起点として培養液交換後の時間経過で遺伝子転写産物資料を採取した。　遺伝子転写産物は定量的リアルタイムPCRで行い、内性対照遺伝子転写産物から算出される指数で補正した。　対象遺伝子は対象遺伝子(リン酸化部位), CREB (Ser133), Erk/MAPK 1/2 (Thr185/Tyr187), IκBα (Ser32), JNK/SAPK1 (Thr183/Tyr185), p38/SAPK2A/B (Thr180/Tyr182), p70 S6 Kinase (Thr412), STAT3 (Ser727), STAT5A/B (Tyr694/699)などである。　IP-10に加えて研究初期段階で得た蛋白質血清中濃度測定を行った。対象は病態の異なる炎症性疾患群と連結不能な環境で検討を行った。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

計画通りに進行している。

Strategy for Future Research Activity

計画の通りに進行する。

Causes of Carryover

複数回の繰り返し確認がおおむね順調に進行したため。

Expenditure Plan for Carryover Budget

計画通りに進行する。

Research Products

• [Journal Article] Distinguishing the cerebrospinal fluid cytokine profile in neuropsychiatric systemic lupus erythematosus from other autoimmune neurological diseases. (2015)
  • Author(s): Ichinose K, Arima K, Ushigusa T, Nishino A, Nakashima Y, Suzuki T, Horai Y, Nakajima H, Kawashiri SY, Iwamoto N, Tamai M, Nakamura H, Origuchi T, Motomura M, Kawakami A.
  • Journal Title: Clin Immunol. Volume: 157 Pages: 114-120
  • DOI: 10.1016/j.clim.2015.01.010.
  • Peer Reviewed
• [Journal Article] Association between the hemoglobin levels and hypertension in relation to the BMI status in a rural Japanese population: the Nagasaki Islands Study. (2015)
  • Author(s): Shimizu Y, Nakazato M, Sekita T, Kadota K, Arima K, Yamasaki H, Takamura N, Aoyagi K, Maeda T.
  • Journal Title: Intern Med. Volume: 53 Pages: 435-440
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association between hemoglobin A1c and carotid atherosclerosis in rural community-dwelling elderly Japanese men. (2015)
  • Author(s): Shimizu Y, Nakazato M, Sato S, Koyamatsu J, Yamanashi H, Nagayoshi M, Kadota K, Hayashida N, Yamasaki H, Kusano Y, Takamura N, Aoyagi K, Maeda T.
  • Journal Title: J Physiol Anthropol. Volume: 34 Pages: 16-17
  • DOI: 10.1186/s40101-015-0054-6.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Risk factors of adverse events during treatment in elderly patients with rheumatoid arthritis: an observational study. (2015)
  • Author(s): Iwanaga N, Arima K, Terada K, Ueki Y, Horai Y, Suzuki T, Nakashima Y, Kawashiri SY, Ichinose K, Tamai M, Nakamura H, Aoyagi K, Kawakami A, Origuchi T.
  • Journal Title: Int J Rheum Dis. Volume: 0 Pages: 0
  • DOI: 10.1111/1756-185X.12348
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Upregulation of Thrombospondin 1 Expression in Synovial Tissues and Plasma of Rheumatoid Arthritis: Role of Transforming Growth Factor-β1 toward Fibroblast-like Synovial Cells. (2015)
  • Author(s): Suzuki T, Iwamoto N, Yamasaki S, Nishino A, Nakashima Y, Horai Y, Kawashiri SY, Ichinose K, Arima K, Tamai M, Nakamura H, Origuchi T, Miyamoto C, Osaki M, Ohyama K, Kuroda N, Kawakami A.
  • Journal Title: J Rheumatol. Volume: 0 Pages: 0
  • Peer Reviewed
• [Journal Article] Successful treatment of Schnitzler syndrome with cyclosporine. (2014)
  • Author(s): Nakajima K, Takahashi M, Yamamoto M, Takahashi A, Sano S, Kodama H, Arima K,
  • Journal Title: Int J Dermatol. Volume: 53 Pages: e361-e363
  • DOI: 10.1111/ijd.12300
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Accuracy of spinal curvature assessed by a computer-assisted device and anthropometric indicators in discriminating vertebral fractures among individuals with back pain. (2014)
  • Author(s): Mizukami S, Abe Y, Tsujimoto R, Arima K, Kanagae M, Chiba G, Aoyagi K.
  • Journal Title: Osteoporos Int. Volume: 25 Pages: 1727-1734
  • DOI: 10.1007/s00198-014-2680-y
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Synovial inflammation assessed by ultrasonography correlates with MRI-proven osteitis in patients with rheumatoid arthritis. (2014)
  • Author(s): Kawashiri SY, Suzuki T, Nakashima Y, Horai Y, Okada A, Nishino A, Iwamoto N, Ichinose K, Arima K, Tamai M, Nakamura H, Origuchi T, Uetani M, Aoyagi K, Eguchi K, Kawakami A.
  • Journal Title: Rheumatology (Oxford) Volume: 53 Pages: 1452-1456
  • DOI: 10.1093/rheumatology/keu034
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Associations between renal impairment and anemia in older, rural Japanese men: the Nagasaki Island study. (2014)
  • Author(s): Shimizu Y, Sato S, Koyamatsu J, Yamanashi H, Nagayoshi M, Kadota K, Tamai M, Arima K, Yamasaki H, Kusano Y, Takamura N, Maeda T.
  • Journal Title: J Physiol Anthropol. Volume: 33 Pages: 7-8
  • DOI: 10.1186/1880-6805-33-7
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Height and drinking status in relation to risk of anemia in rural adult healthy Japanese men: the Nagasaki Islands study. (2014)
  • Author(s): Shimizu Y, Nakazato M, Sekita T, Kadota K, Miura Y, Arima K, Yamasaki H, Goto H, Takamura N, Aoyagi K, Maeda T.
  • Journal Title: Aging Male. Volume: 23 Pages: 1-6
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Combination of MRI-detected bone marrow oedema with 2010 rheumatoid arthritis classification criteria improves the diagnostic probability of early rheumatoid arthritis. (2014)
  • Author(s): Tamai M, Kita J, Nakashima Y, Suzuki T, Horai Y, Okada A, Koga T, Kawashiri SY, Iwamoto N, Ichinose K, Arima K, Yamasaki S, Nakamura H, Origuchi T, Uetani M, Fukushima A, Aoyagi K, Eguchi K, Kawakami A.
  • Journal Title: Ann Rheum Dis. Volume: 73 Pages: 2219-2220
  • DOI: 10.1136/annrheumdis-2013-205074
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mental health problems and influencing factors in Japanese women 4 months after delivery. (2014)
  • Author(s): Yamamoto N, Abe Y, Arima K, Nishimura T, Akahoshi E, Oishi K, Aoyagi K.
  • Journal Title: J Physiol Anthropol. Volume: 33 Pages: 32-33
  • DOI: 10.1186/1880-6805-33-32
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Direct Infection of Primary Salivary Gland Epithelial Cells by Human T Lymphotropic Virus Type I in Patients With Sjögren's Syndrome. (2014)
  • Author(s): Nakamura H, Takahashi Y, Yamamoto-Fukuda T, Horai Y, Nakashima Y, Arima K, Nakamura T, Koji T, Kawakami A.
  • Journal Title: Arthritis Rheumatol. Volume: 67 Pages: 1096-1106
  • DOI: 10.1002/art.39009
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Epidemiology of Kienböck's disease in middle-aged and elderly Japanese women. (2014)
  • Author(s): Tsujimoto R, Maeda J, Abe Y, Arima K, Tomita M, Koseki H, Kaida E, Aoyagi K, Osaki M.
  • Journal Title: Orthopedics. Volume: 38 Pages: e14-e18
  • DOI: 10.3928/01477447-20150105-54
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] LONGITUDINAL ASSOCIATIONS BETWEEN PAINFUL KNEE OSTEOARTHRITIS AND DIFFICULTIES IN PHYSICAL FUNCTIONING AMONG COMMUNITY-DWELLING WOMEN (2015)
  • Author(s): K. Arima, T. Nishimura, Y. Abe, K. Aoyagi
  • Organizer: Annual European Congress of Rheumatology 2015
  • Place of Presentation: Italy, Rome
  • Year and Date: 2015-06-10 – 2015-06-15
• [Remarks] 長崎大学大学院医歯薬学総合研究科医療科学専攻公衆衛生学分野のホームページ
  • URL: http://www.med.nagasaki-u.ac.jp/public-h/