Physiological and pathological roles of inflammation system in placenta during pregnancy.

• Project/Area Number: 20591907
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: The University of Tokyo
• Principal Investigator: FUJII Tomoyuki The University of Tokyo, 医学部附属病院, 准教授 (40209010)
• Co-Investigator(Kenkyū-buntansha): KAWANA Kei 東京大学, 医学部附属病院, 助教 (60311627) ; 兵藤 博信 東京大学, 医学部・附属病院, 助教 (00436495)
• Co-Investigator(Renkei-kenkyūsha): HYODO Hironobu 東京大学, 医学部附属病院, 助教 (00436495)
• 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 妊娠 / 胎盤 / 炎症 / CD1d / 不育症 / 抗リン脂質抗体 / invariant NKT / Interleukin-12 / 絨毛細胞 / オートタキシン

Research Abstract

To clarify the physsiological and pathological roles of inflammation system in placenta during pregnancy, we investigated the roles of CD1d antigen on trophoblasts and of lysophosphatidic acid (LPA) system in placenta. The decrease of CD1d expression on cytotrophoblasts with extravillous trophoblast (EVT) differentiation was induced via transforming growth factor (TGF)-・ secretion by trophoblasts. β_2-glycoprotein I (β_2GPI)-dependent anti-phospholipid antibody induced interleukin-12 release from trophoblasts via recognition of β_2GPI bound to phosphatidylserine on CD1d on trophoblasts, which might cause pregnancy loss via inflammatory mechanism.
Trophoblasts expressed the major lysophosphatidic acid (PLA) producing enzyme, autotaxin (ATX). RNA amounts of ATX in placenta tissues increased with gestational weeks. The serum concentration of ATX protein was higher in patients with preterm labor than that in normal pregnant women. These results suggest the physiological roles of its bioactive resultant substance, LPA, during pregnancy.

Research Products

• [Journal Article] Expression of autotaxin, an ectoenzyme that produces lysophosphatidic acid, in human placenta. (2009)
  • Author(s): Iwasawa Y, Fujii T, Nagamatsu T, Kawana K, Okudaira S, Miura Tomio A, Hyodo H, Yamashita T, Oda K, Kozuma S, Aoki J, Yatomi Y, Taketani Y
  • Journal Title: Am J Reprod Immunol 62 Pages: 90-95
  • Peer Reviewed
• [Journal Article] Expression of surface CDId in the extravillous trophoblast cells of early gestational placenta is downregulated in a manner dependent on trophoblast differentiation. (2008)
  • Author(s): Matsumoto J, et al.
  • Journal Title: Biochem Biophys Res Commun 371 Pages: 236-241
  • Peer Reviewed
• [Presentation] 妊娠初期における絨毛細胞上のCD1dと脱落膜invariant NKT細胞の相互作用に関する研究 (2010)
  • Author(s): 岩澤有希, 川名敬, 藤井知行, 永松健, 松本順子, 三浦紫保, 山下隆博, 兵藤博信, 上妻志郎, 武谷雄二
  • Organizer: 第62回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2010-04-25
• [Presentation] 妊娠初期における絨毛細胞上のCD1dと脱落膜invariant NKT細胞の相互作用に関する研究 (2010)
  • Author(s): 岩澤有希,川名敬,藤井知行,松本順子,三浦紫保,山下隆博,兵藤博信,上妻志郎,武谷雄二
  • Organizer: 第62回日本産科婦人科学会総会・学術講演会
  • Place of Presentation: 東京
• [Presentation] A novel pathogenic mechanism of recurrent miscarriage associated with β_2glycoprotein I-dependent-antiphospholipid-antibody through the function of CDld. (2009)
  • Author(s): Iwasawa Y, Kawana K, Miura S, Fujii T
  • Organizer: 14^<th> International Congress of Mucosal Immunology
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 2009-07-06
• [Presentation] A possible pathogenic mechanism of recurrent miscarriage associated with β_2glycoprotein I-dependent-antiphospholipid-antibody through the function of CDld. (2009)
  • Author(s): Iwasawa Y, Kawana K, Fujii T, Nagamatsu T, Matsumoto J, Miura S, Hyodo H, Yamashita T, Kozuma S.Taketani Y
  • Organizer: 29^<th> Annual Meeting of American Society for Reproductive Immunology
  • Place of Presentation: Orlando, FL, USA
  • Year and Date: 2009-06-09
• [Presentation] A novel pathogen mechanism of recurrent miscarriage associated with ・2glycoprotein I-dependent antiphospholipid antibody through CD1d on the trophoblast. (2009)
  • Author(s): Iwasawa Y, Kawana K, Miura S, Fujii T
  • Organizer: 14th InternaCongress of Mucosal Immunology.
  • Place of Presentation: Boston, MA, USA
• [Presentation] A possible pathogenic mechanism of recurrent miscarriage associated with・2 glycoprotein I-dependent antiphospholipid antibody through the function of CD1d. (2009)
  • Author(s): Iwasawa Y, Kawana K, Fujii T, Nagamatsu T, Matsumoto J, Miura S, Yamashita T, Hoyodo H, Kozuma S, Taketani Y
  • Organizer: 29th Annual Meeting of The American Society for Reproductive Immunology
  • Place of Presentation: Orlando, FL, USA
• [Presentation] 絨毛細胞上に存在するリン脂質抗原提示分子「CD1d」を介した、・2glycoproteinI依存性抗リン脂質抗体による新規流産メカニズムに関する検討 (2009)
  • Author(s): 岩澤有希,川名敬,藤井知行,永松健,松本順子,三浦紫保,吉田志朗,兵藤博信,山下隆博,上妻志郎,武谷雄二
  • Organizer: 第61回日本産科婦人科学会総会・学術講演会
  • Place of Presentation: 京都
• [Presentation] 絨毛細胞上に存在するリン脂質抗原提示分子「CD1d」を介した、・glycoproteinI依存性抗リン脂質抗体による新規流産メカニズムに関する検討 (2008)
  • Author(s): 岩澤有希、川名敬、藤井知行、永松健、松本順子、三浦紫保、山下隆博、兵藤博信、上妻志郎、武谷雄二
  • Organizer: 第23回日本生殖免疫学会総会・学術集会
  • Place of Presentation: 富山
• [Remarks] ホームページ等