Nucleophosmin: immunoactivity as a novel alarmin

• Project/Area Number: 24659804
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Emergency medicine
• Research Institution: Osaka Institute of Technology
• Principal Investigator: KAWAHARA Ko-ichi 大阪工業大学, 工学部, 教授 (10381170)
• Co-Investigator(Kenkyū-buntansha): MARUYAMA Ikuro 鹿児島大学, 大学院医歯(薬)学総合研究科, 特任教授 (20082282) ; HASHIGUCHI Teruto 鹿児島大学, 大学院医歯(薬)学総合研究科, 教授 (70250917) ; ITO Takashi 鹿児島大学, 大学院医歯(薬)学総合研究科, 特任講師 (20381171)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ヌクレオフォスミン / アラーミン / 免疫活性化 / ファゴサイトーシス / 救急医学 / 敗血症

Research Abstract

Nucleophosmin is a major nucleolar multifunctional protein involved in ribosome biogenesis, centrosome duplication, cell cycle progression, apoptosis, and cell differentiation. Alarmins are endogenous molecules released from activated cells and/or dying cells, which activate the immune system and cause severe damage to cells and tissue organs. Recently, the nucleophosmin is released from endotoxin-stimulated RAW264.7 cells and induces cytokines, suggesting that nucleophosmin might be an alarmin. However, nucleophosmin as a alarmin remains unclear. In this study, we found that the nucleophosmin-stimulated RAW264.7 cells significantly enhanced phagocytosis with flowcytometry. Furthermore, the nuclephosmin enhanced phagocytosis in in a dose-dependent fashion. Our findings suggest that nucleophosmin may be an alarmin.

Research Products

• [Journal Article] Upregulation of non-β Cell-derived Vascular Endothelial Growth FactorA Increases Small Clusters of Insulin producing Cells in the Pancreas. (2014)
  • Author(s): Takenouchi K, Shrestha B, Yamakuchi M, Yoshinaga M, Arimura N, Kawaguchi H, Nagasato T, Feil R, Kawahara K-I, Sakamoto T, Maruyama I, Hashiguchi T.
  • Journal Title: Experimental and Clinical Endocrinology & Diabetes Volume: in press Issue: 05 Pages: 308-15
  • DOI: 10.1055/s-0034-1371811
  • Peer Reviewed / Open Access
• [Journal Article] Comparative evaluation of direct thrombin and factor Xa inhibitors with antiplatelet agents under flow and static conditions : an in vitro flow chamber model (2014)
  • Author(s): Hosokawa K, Ohnishi T, Sameshima H, Miura N, Koide T, Maruyama I, Tanaka KA
  • Journal Title: PLoS One Volume: 9(1) Issue: 1 Pages: 86491-86491
  • DOI: 10.1371/journal.pone.0086491
  • Peer Reviewed
• [Journal Article] Antithrombotic effects of PAR1 and PAR4 antagonists evaluated under flow and static conditions (2014)
  • Author(s): Hosokawa K, Ohnishi T, Miura N, Sameshima H, Koide T, Tanaka KA, Maruyama I
  • Journal Title: Thromb Res Volume: 133(1) Issue: 1 Pages: 66-72
  • DOI: 10.1016/j.thromres.2013.10.037
  • Peer Reviewed
• [Journal Article] Recombinant thrombomodulin protects mice against histone-induced lethal thromboembolism. (2013)
  • Author(s): Nakahara M, Ito T, et al.
  • Journal Title: PLoS One Volume: 8(9) Issue: 9 Pages: 75961-75961
  • DOI: 10.1371/journal.pone.0075961
  • Peer Reviewed
• [Journal Article] Potential of the angiotensin receptor blockers (ARBs) telmisartan, Irbesartan, and candesartan for inhibiting the HMGB1/RAGE axis in prevention and acute treatment of stroke. (2013)
  • Author(s): Kikuchi K, Tancharoen S, Ito T, Morimoto-Yamashita Y, Miura N, Kawahara K, MaruyamaI, Murai Y, Tanaka E
  • Journal Title: Int. Mol. Sci. Volume: 14 Issue: 9 Pages: 18899-18924
  • DOI: 10.3390/ijms140918899
  • Peer Reviewed
• [Journal Article] Preventive effects of Morus alba L. anthocyanins on diabetes in Zucker diabetic fatty rats (2013)
  • Author(s): Sarikaphuti A, Nararatwanchai T, Hashiguchi T, Ito T, Thaworanunta S, Kikuchi K, Oyama Y, Maruyama I, Tancharoen S
  • Journal Title: Exp Ther Med Volume: 6(3) Pages: 689-695
  • URL: http://www.spandidos-publications.com/etm/
  • Peer Reviewed
• [Journal Article] Saturated fatty acid palmitate induces extracellular release of histone H3 : a Possible mechanistic basis for high-fat diet-induced inflammation and thrombosis. (2013)
  • Author(s): Shrestha C, Ito T, et al.
  • Journal Title: Biochemical and biophysical research communications Volume: 437(4) Issue: 4 Pages: 573-578
  • DOI: 10.1016/j.bbrc.2013.06.117
  • Peer Reviewed
• [Journal Article] Coagulation activity and white thrombus formation in the microminipig (2013)
  • Author(s): Miura N, Kawaguchi H, Nagasato T, Yamada T, Ito T, Izumi H, Shameshima H, Miyoshi N, Tanimoto A, Maruyama I
  • Journal Title: In Vivo Volume: 27(3) Pages: 357-61
  • URL: http://iv.iiarjournals.org
  • Peer Reviewed
• [Journal Article] Hemoadsorption of high-mobility group box chromosomal protein 1 using a column for large animals (2013)
  • Author(s): Nishiyama R, Shinoda M, Tanabe M, Oshima G, Takano K, Miyasho T, Fuchimoto Y, Yamada S, Inoue T, Shimada K, Suda K, Tanaka M, Hayashida T, Yagi H, Kitago M, Obara H, Itano O, Takeuchi H, Kawachi S, Maruyama I, Kitagawa Y
  • Journal Title: Eur Surg Res Volume: 51(3-4) Issue: 3-4 Pages: 181-90
  • DOI: 10.1159/000357563
  • Peer Reviewed / Open Access
• [Journal Article] Immunohistochemical expression of thrombomodulin in vestibular schwannoma (2013)
  • Author(s): Yamahata H, Yunoue S, Tokimura H, Hanaya R, Hirano H, Tokudome M, Karki P, Yonezawa H, Sugata S, Kawahara K, Maruyama I, Arita K
  • Journal Title: Brain Tumor Pathol Volume: 30(1) Issue: 1 Pages: 28-33
  • DOI: 10.1007/s10014-012-0095-z
  • Peer Reviewed
• [Journal Article] Analysing responses to aspirin and clopidogrel by measuring platelet thrombus formation under arterial flow conditions (2013)
  • Author(s): Hosokawa K, Ohnishi T, Sameshima H, Miura N, Ito T, Koide T, Maruyama I
  • Journal Title: Thromb Haemost Volume: 109(1) Issue: 01 Pages: 102-11
  • DOI: 10.1160/th12-06-0441
  • Peer Reviewed
• [Journal Article] Paucity of CD34-positive cells and increased expression of high-mobility group box 1 in coronary thrombus with type 2 diabetes mellitus. (2012)
  • Author(s): Yamashita A, Nishihira K, Matsuura Y, Ito T, Kawahara K, Hatakeyama K, Hashiguchi T, Maruyama I, Yagi H, Matsumoto M, Fujimura Y, Kitamura K, Shibata Y, Asada Y.
  • Journal Title: Atherosclerosis. Volume: 224 Issue: 2 Pages: 511-514
  • DOI: 10.1016/j.atherosclerosis.2012.07.027
  • Peer Reviewed
• [Journal Article] Efficacy of MK615 for the treatment of patients with liver disorders (2012)
  • Author(s): Hokari A, Ishikawa T, Tajiri H, Matsuda T, Ishii O, Matsumoto N, Okuse C, Takahashi H, Kurihara T, Kawahara K, Maruyama I, Zeniya M
  • Journal Title: World J Gastroenterol Volume: 18(31) Issue: 31 Pages: 4118-26
  • DOI: 10.3748/wjg.v18.i31.4118
  • Peer Reviewed
• [Journal Article] Secondary prevention of stroke : Pleiotropic effects of optimal oral pharmacotherapy (2012)
  • Author(s): Kikuchi K, Kawahara K, Miura N, Ito T, Morimoto Y, Tancharoen S, Takeshige N, Uchikado H, Sakamoto R, Miyagi N, Kikuchi C, Iida N, Shiomi N, Kuramoto T, Hirohata M, Maruyama I, Morioka M, Tanaka E
  • Journal Title: Exp Ther Med Volume: 4(1) Pages: 3-7
  • URL: http://www.spandidos-publications.com/etm/
  • Peer Reviewed
• [Journal Article] MK615, a Prunus mume Steb.Et Zucc (Ume) extract, attenuates the growth of A375 melanoma cells by inhibiting the ERK1/2-Id-1 pathway (2012)
  • Author(s): Tada K
  • Journal Title: Phytother Res Volume: (in press) Issue: 6 Pages: 833-838
  • DOI: 10.1002/ptr.3645
  • Peer Reviewed
• [Journal Article] Granulocyte and monocyte adsorption apheresis as an effective treatment for Reiter disease (2012)
  • Author(s): Yoshifuku A, Oyama K, Ibusuki A, Kawasaki M, Sakanoue M, Matsushita S, Kawai K, Kawahara K, Maruyama I, Kanekura T
  • Journal Title: Clin Exp Dermatol Volume: 37(3) Issue: 3 Pages: 241-4
  • DOI: 10.1111/j.1365-2230.2011.04181.x
  • Peer Reviewed
• [Presentation] イチゴエキスはHMGB1の放出を抑制する (2013)
  • Author(s): 大池加恵、上村龍平、丸山征郎、川原幸一
  • Organizer: 2013年度日本生物高分子学会
  • Place of Presentation: 大阪
  • Year and Date: 2013-11-20
• [Presentation] マクロファージにおけるプロスタグランジン合成酵素の誘導 (2013)
  • Author(s): 井上智博、川原幸一、松村潔
  • Organizer: 2013年度日本生物高分子学会
  • Place of Presentation: 大阪
  • Year and Date: 2013-11-20
• [Presentation] 炎症に起因する血栓症の病態解明~新規メディエーターとしてのPAMPs・DAMPs~ (2013)
  • Author(s): 伊藤隆史
  • Organizer: 第35回血栓止血学会
  • Place of Presentation: 山形
  • Year and Date: 2013-05-30
• [Presentation] イチゴの新規機能 : HMGB1放出抑制 (2012)
  • Author(s): 上村龍平、大池加恵、丸山征郎、川原幸一
  • Organizer: 第85回生化学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-15
• [Presentation] イチゴの新規機能 : HMGB1放出抑制 (2012)
  • Author(s): 上村龍平、大池加恵、丸山征郎、川原幸一
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-14
• [Presentation] イチゴの新規機能 : HMGB1放出抑制 (2012)
  • Author(s): 上村龍平、大池加恵、丸山征郎、川原幸一
  • Organizer: 第51回日本栄養・食糧学会近畿支部大会
  • Place of Presentation: 兵庫
  • Year and Date: 2012-10-20
• [Book] 別冊BIO Clinica慢性炎症と疾患骨髄-末梢血による炎症の制御と修飾血小板-好中球のサティリティズムと炎症 (2013)
  • Author(s): 大池加恵、川原幸一
  • Publisher: 北隆館
• [Book] 特集PAMPs/DAMPsと血栓症DIC NETsとヒストンThrombosis medicine 3(4) (2013)
  • Author(s): 大池加恵、川原幸一
  • Publisher: 先端医学社
• [Book] 特集"自然"炎症と凝固・血小板系のクロストーク(第4回) NETs(Neutorophil Extracellular Traps)と血栓症Thrombosis medicine 2(3) (2012)
  • Author(s): 上村龍平、川原幸一
  • Publisher: 先端医学社