Development of a new diagnostic system of inflammatory diseases by measuring S100A8/A9・cytokine complexes

• Project/Area Number: 20590567
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Kyoto University
• Principal Investigator: IKEMOTO Masaki Kyoto University, 大学院・医学研究科, 准教授 (80144385)
• Co-Investigator(Kenkyū-buntansha): UEMOTO Shinji 京都大学, 大学院・医学研究科, 教授 (40252449) ; EGAWA Haruto 朝日大学, 歯学部, 教授 (40293865)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: S100蛋白 / マクロファージ / 好中球 / 拒絶反応 / 急性炎症 / サイトカイン / S100A8/A9 / フィブロネクチン / アンチトロンビンIII / プラスミノーゲン / S100A8 / A9 / Neutrophils / Macrophages / Cytokines / Acute inflammation / Inflammatory marker / Lipopolysaccharide / Liver damage / Neutrophil / Macrophage

Research Abstract

We found that S100A8/A9 non-specifically bind with fibronectin (h-FN), and that both the two protein exist on surface membrane of neutrophils and monocytes. The h-FN could be conclusively transported with S100A8/A9 in blood and/or on immunological cells, and effectively prevent further attack by various internal oxidants or repair damaged liver tissue in vivo. When recombinant human S100A8 was intravenously injected in the rats with LPS-induced liver damage, not only expression of r-S100A9 but also the activities of AST, ALT and LD significantly went down in comparison with those of the rats with liver damage, strongly suggested that the r-S100A8 could serve as a regulator of acute inflammatory reaction in the rats with LPS-induced damage. Immunohistochemistry provided interesting microscopic images, in which much r-S100A8 and r-S100A9 were observed in many macrophages in the heart tissues of rats with experimental autoimmune myocarditis. In addition, macrophages were positive for not only CD68 antigen but also r-S100A8 and/or r-S100A9 proteins, strongly suggesting active condition of the macrophages in inflamed areas of the heart tissues with EAM. Therefore, r-S100A8 and r-S100A9 in macrophages should be novel indexes for active condition of the cells in the EAM rats.

Research Products

• [Journal Article] Dynamic mobility of immunological cells expressing S100A8 and S100A9 in vivo : a variety of functional roles of the two proteins as regulators inacute inflammatory reaction. (2011)
  • Author(s): Koike A, Arai S, Yamada S, Nagae A, Saita N, ItohH, Uemoto S, Totani M, Ikemoto M.
  • Journal Title: Inflammation in press
  • Peer Reviewed
• [Journal Article] S100A8/A9 complex new biomarker in prediction ofmortality iasn ealderly patients with severe heart failure. (2011)
  • Author(s): Li-Ping Ma, Espen Haugen Masaki Ikemoto, Masatoshi Fujita, Fumio Terasaki, Michael Fu.
  • Journal Title: Int J Cardiol in press
  • Peer Reviewed
• [Journal Article] Dynamic mobility of immunological cells expressing S100A8 and S100A9 in vivo : a variety of functional roles of the two proteins as regulators in acute inflammatory reaction (2011)
  • Author(s): Koike A, Arai S, Yamada S, Nagae A, Saita N, Itoh H, Uemoto S, Totani M, Ikemoto M
  • Journal Title: Inflammation Volume: (in press)
  • Peer Reviewed
• [Journal Article] S100A8/A9 complex as a new biomarker in prediction of mortality in elderly patients with severe heart failure (2011)
  • Author(s): Li-Ping Ma, Espen Haugen, Masaki Ikemoto, Masatoshi Fujita, Fumio Terasaki, Michael Fu
  • Journal Title: Int J Cardiol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Identification of serum proteins that bind with S100A8, S100A9 and S100A8/A9 : clinical significance of using proteins for monitoring the postoperative condition of liver recipients. (2010)
  • Author(s): Namura T, Arai S, Okawa K, Koike A, Yamada S, Saita N, Nagae A, Itoh H, Totani M, Uemoto S, Ikemoto M.
  • Journal Title: Clin Chim Acta Vol.411 Pages: 1766-1773
  • NAID: 120002647318
  • Peer Reviewed
• [Journal Article] Possible mechanism for regulation of inflammatory responses with the S100A8/A9 protein. (2010)
  • Author(s): Namura T, Arai S, Koike A, Yamada S, Totani M, Ikemoto M.
  • Journal Title: Rinsho Byori Vol.58 Pages: 651-657
  • NAID: 10027751785
  • Peer Reviewed
• [Journal Article] Enhanced Expression of the S100A8/A9 Complex in AcuteMyocardial Infraction Patients. (2010)
  • Author(s): Katashima T, Naruko T, Terasaki F, Fujita M, Otsuka K, Murakami S, Sato S, Hiroe M, Ikura Y, Ueda M, Ikemoto M, Kitaura Y.
  • Journal Title: Circ J Vol.74 Pages: 741-748
  • Peer Reviewed
• [Journal Article] Identification of serum proteins that bind with S100A8, S100A9 and S100A8/A9: clinincal significance of using proteins for monitoring the Postoperative condition of liver recipients (2010)
  • Author(s): Namura T, Arai S, Okawa K, Koike A, Yamada S, Saita N, Nagae A, Itoh H, Totani M, Uemoto S, Ikemoto M
  • Journal Title: Clin Chim Acta Volume: Vol.411 Pages: 1766-1773
  • Peer Reviewed
• [Journal Article] Possible mechanism for regulation of inflammatory responces with the S100A8/A9 protein (2010)
  • Author(s): Namura T, Arai S, Koike A, Yamada S, Totani M, Ikemoto M
  • Journal Title: Rinsho Byori Volume: Vol.58 Pages: 651-657
  • Peer Reviewed
• [Journal Article] Enhanced Expression of the S100A8/A9 Complex in Acute Myocardial Infarction Patients (2010)
  • Author(s): Katashima T, Naruko T, Terasaki F, Fujita M, Otsuka K, Murakami S, Sato S, Hiroe M, Ikura Y, Ueda M, Ikemoto M, Kitaura Y
  • Journal Title: Circ J Volume: Vol.74 Pages: 741-748
  • NAID: 10026472579
  • Peer Reviewed
• [Journal Article] Enhanced Expression of the S100A8/A9 Complex in Acute Myocardila Infraction Patients (2010)
  • Author(s): Takashi Katashima, Takahiko Naruko, Fumio Terasaki, Masatoshi Fujita, Kaoru Otsuka, Shougo Murakami, Akira Sato, Michiaki Hiroe, Yoshihiro Ikura, Makiko Ueda, Masaki Ikemoto, Yasushi Kitaura
  • Journal Title: Circulation Jouranl (in press)
  • Peer Reviewed
• [Journal Article] Suppression of inflammation in rat autoimmunemyocarditis by S100A8/A9 through modulation ofthe proinflammatory cytokine network. (2009)
  • Author(s): Otsuka K, Terasaki F, Ikemoto M, Fujita M, Tsukada B, Takashima T, Kanzaki Y, Sohmiya K,Kono T, Toko H, Fujita M, Kitaura Y l.
  • Journal Title: Eur J of Heart Failure Vol.10 Pages: 1093-1101
  • Peer Reviewed
• [Journal Article] Possibility of formation ofthe S100A8/A9 proinflammatory cytokinecomplexes in vivo in acute inflammation and theirfunctional roles. (2009)
  • Author(s): Ishihara K, Namura T, Murayama H, Arai S, Totani M, Ikemoto M.
  • Journal Title: Rinsho Byori Vol.57 Pages: 324-331
  • Peer Reviewed
• [Journal Article] Suppression of inflmmation in rat autoimmune myocarditis by S100A8/A9 through modulation of the proinflammnatory cytokine network (2009)
  • Author(s): Kaoru Otsuka, Fumio Terasaki, Masaki Ikemoto, Shuichi Fujita, Bin Tsukada, Takashi Katashima, Yumiko Kanzaki, Koichi Sohmiya, Tatsuji Kono, Haruhiro Toko, Masatoshi Fujita, Yasushi Kitaura
  • Journal Title: European Journal of Heart Failure Voll. 11 Pages: 1-9
  • Peer Reviewed
• [Journal Article] 急性炎症期におけるS100A8/A9-炎症性サイトカイン複合体形成の可能性及びその機能的役割について (2009)
  • Author(s): 石原佳依, 南村知代, 村山寛, 荒井智, 戸谷誠之, 池本正生
  • Journal Title: 臨床病理 Vol. 57(in press)
  • Peer Reviewed
• [Journal Article] Increased serum levels and expression ofS100A8/A9 complex in infiltrated neutrophils inatherosclerotic plaque of unstable angina. (2008)
  • Author(s): Miyamoto S, Ikemoto M, Naruko T, Itoh A, Tamaki S, Nohara R, Terasaki F, Sasayama S, Fujita M.
  • Journal Title: Heart Vol.94 Pages: 1002-1007
  • Peer Reviewed
• [Journal Article] Superiority of serum type-I arginase and ornithinecarbamoyltransferase in the detection of toxicant-induced acute hepatic injury in rats. (2008)
  • Author(s): Murayama H, Ikemoto M, Fukuda Y, Nagata A.
  • Journal Title: Clin Chim Acta Vol.391 Pages: 31-35
  • Peer Reviewed
• [Presentation] S100A8とS100A9による炎症反応調節機構及び臨床的意義について (2010)
  • Author(s): 小池阿木子, 山田幸子, 南村知代, 荒井智、斎田尚子, 永江亜紀子, 戸谷誠之, 池本正生
  • Organizer: 第57回臨床検査医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-11
• [Presentation] S100タンパク質に結合する血清中タンパク質の同定-肝移植後の監視における臨床的意義について- (2010)
  • Author(s): 山田幸子, 小池阿木子, 南村知代, 荒井智、斎田尚子, 永江亜紀子, 戸谷誠之, 池本正生
  • Organizer: 第57回臨床検査医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-10
• [Presentation] S100A8とS100A9による炎症反応調節機構及び臨床的意義について (2010)
  • Author(s): 小池阿木子、山田幸子、南村知代、荒井智、斎田尚子、永江亜紀子、戸谷誠之、池本正生
  • Organizer: 第57回臨床検査医学会学術集会
  • Place of Presentation: 京王プラザホテル(東京)
• [Presentation] S100タンパク質に結合する血清中タンパク質の同定-肝移植後の監視における臨床的意義について- (2010)
  • Author(s): 山田幸子、小池阿木子、南村知代、荒井智、斎田尚子、永江亜紀子、戸谷誠之、池本正生
  • Organizer: 第57回臨床検査医学会学術集会
  • Place of Presentation: 京王プラザホテル(東京)
• [Presentation] S100A8/A9による炎症反応調節機構及びその臨床的意義について (2009)
  • Author(s): 南村知代, 山田幸子, 小池阿木子, 荒井智, 戸谷誠之, 池本正生
  • Organizer: 第56回臨床検査医学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2009-08-27
• [Presentation] S100A8/A9による炎症反応調節機構及びその臨床的意義について (2009)
  • Author(s): 南村知代, 山田幸子, 小池阿木子, 荒井智, 戸谷誠之, 池本正生
  • Organizer: 第56回臨床検査医学会学術集会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2009-08-27
• [Presentation] S100A8/A9・炎症性サイトカイン複合体の新しいバイオマーカーとしての臨床的意義について (2008)
  • Author(s): 石原佳依, 南村知代, 村山寛, 戸谷誠之, 池本正生
  • Organizer: 第48回日本臨床化学会年次学術集会
  • Place of Presentation: 静岡
  • Year and Date: 2008-08-30
• [Presentation] S100A8/A9・炎症性サイトカイン複合体の新しいバイオマーカーとしての臨床的意義について (2008)
  • Author(s): 石原佳依, 南村知代, 村山寛, 戸谷誠之, 池本正生
  • Organizer: 第48回日本臨床化学会年次学術集会
  • Place of Presentation: 静岡文化芸術大学
  • Year and Date: 2008-08-30