Development of a plan of the new C5a receptor antagonist

• Project/Area Number: 26462863
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Hyogo Medical University
• Principal Investigator: Nishiura Hiroshi 兵庫医科大学, 医学部, 助教 (90284760)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: RP S19 / C5a受容体 / アポトーシス / マクロファージ / 貪食処理 / 急性炎症 / アゴニスト / アンタゴニスト / デルタラクトフェリン / アネキシンA3 / リボソームタンパク質S19 / 好中球 / p38MAPK / 二次元電気泳動 / TOF-MAS

Outline of Final Research Achievements

All apoptotic cells express C5a receptor or produce and release its antagonist/agonist ligand ribosomal protein S19 (RP S19) polymer. When one of binding motives of RP S19 polymer binds to the C5a receptor on apoptotic cells in an autocrine manner, a lifespan of apoptotic cells is shorten through an activation of an apoptosis-inducing transcription factor delta-type lactoferrin. Next, another binding motives of RP S19 polymer bind to the C5a receptor on macrophages in an paracrine manner, a phagocytic time of apoptotic cells is shorten through an activation of a calcium channel-opening factor wild-type annexin A3.

Research Products

• [Journal Article] RP S19 C-terminal peptide trimer acts as a C5a receptor antagonist (2017)
  • Author(s): Nishiura H., Kawakami T., Kawabe M., Kato-Kogoe N., Yamada N., Nakasho K., and Yamanegi K.
  • Journal Title: Biochem. Biophys. Rep. Volume: 10 Pages: 70-76
  • DOI: 10.1016/j.bbrep.2016.05.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The roles of a ribosomal protein S19 polymer in a mouse model of carrageenan-induced acute pleurisy. (2017)
  • Author(s): Yamanegi K, Kawakami T, Yamada N, Kumanishi S, Futani H, Nakasho K, Nishiura H.
  • Journal Title: Immunobiology Volume: 222(5) Issue: 5 Pages: 738-750
  • DOI: 10.1016/j.imbio.2017.02.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The roles of ribosomal protein S19 C-terminus in a shortened neutrophil lifespan through delta lactoferrin. (2015)
  • Author(s): Nishiura H, Yamanegi K, Kawabe M, Kato-Kogoe N, Yamada N, Nakasho K.
  • Journal Title: Immunobiology. Volume: 220(9) Issue: 9 Pages: 1085-1092
  • DOI: 10.1016/j.imbio.2015.05.006
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] New aspects of the C5a receptor (2014)
  • Author(s): Hiroshi Nishiura, Kiyoshi Ohura
  • Journal Title: Advances in Bioscience and Biotechnology Volume: 5 Issue: 01 Pages: 54-63
  • DOI: 10.4236/abb.2014.51009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Annexin A3 plays a role in cytoplasmic calcium oscillation by extracellular calcium in the human promyelocytic leukaemia HL-60 cells differentiated by phorbol-12-myristate-13-acetate (2014)
  • Author(s): Hiroshi Nishiura, Koji Yamanegi, Mutsuki Kawabe, Nahoko Kato-Kogoe, Naoko Yamada, Keiji Nakasho
  • Journal Title: Experimental and Molecular Pathology Volume: 97 Issue: 2 Pages: 241-246
  • DOI: 10.1016/j.yexmp.2014.07.010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Expression of interleukin-34 and colony stimulating factor-1 in the stimulated periodontal ligament cells with tumor necrosis factor-α (2014)
  • Author(s): Kawabe M, Ohyama H, Kato-Kogoe N, Yamada N, Yamanegi K, Nishiura H, Hirano H, Kishimoto H, Nakasho K.
  • Journal Title: Med Mol Morphol Volume: 25 Issue: 3 Pages: 54-68
  • DOI: 10.1007/s00795-014-0094-8
  • Peer Reviewed / Open Access
• [Presentation] Condition of Gln137Gly RP S19 gene knocked-in C57BL/6J female mice (2016)
  • Author(s): Nishiura H., Yamanegi K., Yamada N., and Nakasho K.
  • Organizer: the 26th International Complement Workshop
  • Place of Presentation: ホテル日航金沢(石川県、金沢市)
  • Year and Date: 2016-09-04
• [Presentation] A sjogren’s syndrome-like condition in Gln137Gly RP S19 gene knocked-in C57BL/6J female mice (2016)
  • Author(s): Nishiura H., Yamanegi K., Yamada N., and Nakasho K.
  • Organizer: International Congress of Immunology
  • Place of Presentation: Melboume, Australia
  • Year and Date: 2016-08-21
• [Presentation] A sjogren’s syndrome-like condition in Gln137Gly RP S19 gene knocked-in C57BL/6J female mice (2016)
  • Author(s): Nishiura H.*, Yamanegi K., Yamada N., and Nakasho K.
  • Organizer: International Congress of Immunology
  • Place of Presentation: メルボルン（オ-ストラリア）
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] Gln137Glu変異RP S19遺伝子ノックインマウスの病態 (2016)
  • Author(s): 西浦弘志, 山根木康嗣, 小越菜保子, 中正恵二
  • Organizer: 日本病理学会総会
  • Place of Presentation: 仙台国際センター（宮城県、仙台市）
  • Year and Date: 2016-05-12
• [Presentation] Gln137Glu変異RP S19遺伝子ノックインマウスの病態 (2016)
  • Author(s): 西浦弘志*, 山根木康嗣, 小越菜保子, 中正恵二
  • Organizer: 日本病理学会総会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2016-05-12
• [Presentation] 骨肉腫細胞における低酸素による細胞表面MICAの発現低下 (2015)
  • Author(s): 山田直子*, 山根木康嗣, 小越（加藤）菜保子, 西浦 弘志, 中正 恵二
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸ポートピアアイランド（兵庫県・神戸市）
  • Year and Date: 2015-12-01
• [Presentation] 下顎歯肉に発生した隆起性病変 (2015)
  • Author(s): 山根木康嗣*, 西浦弘志, 小越菜保子, 和唐雅博, 岡村友玄, 富永和也, 西川哲成, 田中昭男
  • Organizer: 日本臨床口腔病理学会総会
  • Place of Presentation: 北海道大学学術交流会館（北海道・札幌市）
  • Year and Date: 2015-07-29
• [Presentation] 部分的細胞恒常性維持機構欠損のC57BL/6Jマウス病態への影響 (2015)
  • Author(s): 西浦弘志*, 山根木康嗣
  • Organizer: 日本臨床口腔病理学会総会
  • Place of Presentation: 北海道大学学術交流会館（北海道・札幌市）
  • Year and Date: 2015-07-29
• [Presentation] 上顎に発生した骨肉腫の1例. (2015)
  • Author(s): 山根木康嗣*, 西浦弘志, 小越菜保子, 川邊睦記, 首藤敦史, 野口一馬, 岸本裕充， 中正恵二.
  • Organizer: 日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-04-30
• [Presentation] 転移性エナメル上皮種の鑑別法 (2015)
  • Author(s): 西浦弘志*, 山根木康嗣, 小越菜保子, 中正恵二.
  • Organizer: 日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-04-30