The research of imflammasome system in preeclampsia using STOX1 transgenic mice.

• Project/Area Number: 26462498
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Jichi Medical University
• Principal Investigator: SUZUKI HIROTADA 自治医科大学, 医学部, 講師 (90406116)
• Co-Investigator(Kenkyū-buntansha): 大口 昭英 自治医科大学, 医学部, 教授 (10306136) ; 白砂 孔明 東京農業大学, 農学部, 准教授 (20552780)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 妊娠高血圧症候群 / インフラマソーム / 炎症

Outline of Final Research Achievements

We produced the STOX1 transgenic mice. The pregnant mice had miscarriages all the times. They didn’t work out as the model mice of preeclampsia. In human placental cell culture, inflammatory cytokines were increased in the culture with the sera of preeclampsia women and induced apoptosis in the culture. Cell free DNA extracted from the sera of preeclampsia women induced inflammation in the human placental cell culture. Cell free DNA was secreted in the placental tissues of preeclampsia more than of normal pregnancy. Toll like receptor 9 recognizes extracellular DNA. The genes and proteins of toll like receptor 9 increased in the culture with the sera of preeclampsia women. It may be related to the system.

Research Products

• [Journal Article] Oxygen concentration modulates cellular senescence and autophagy in human trophoblast cells (2018)
  • Author(s): Seno K, Tanikawa N, Takahashi H, Ohkuchi A, Suzuki H, Matsubara S, Iwata H, Kuwayama T, Shirasuna K
  • Journal Title: Am J Reprod Immunol Volume: 79 Issue: 6
  • DOI: 10.1111/aji.12826
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Advanced glycation end products regulate interleukin-1β production in human placenta (2017)
  • Author(s): Seno K, Sase S, Ozeki A, Takahashi H, Ohkuchi A, Suzuki H, Matsubara S, Iwata H, Kuwayama T, Shirasuna K
  • Journal Title: Journal of Reproduction and Development Volume: 63 Issue: 4 Pages: 401-408
  • DOI: 10.1262/jrd.2017-032
  • NAID: 130005982808
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed / Open Access
• [Journal Article] Advanced glycation end products regulate interleukin-1β production in human placenta. (2017)
  • Author(s): Seno K, Sase S, Ozeki A, Takahashi H, Ohkuchi A, Suzuki H, Matsubara S, Iwata H, Kuwayama T, Shirasuna K.
  • Journal Title: J Reprod Dev Volume: 印刷中
  • NAID: 130005982808
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] AGEs and HMGB1 increase inflammatory cytokine production from human placental cells, resulting in an enhancement of monocyte migration. (2016)
  • Author(s): Shirasuna K, Seno K, Ohtsu A, Shiratsuki S, Ohkuchi A, Suzuki H, Matsubara S, Nagayama S, Iwata H, Kuwayama T.
  • Journal Title: Am J Reprod Immunol Volume: 75 Pages: 557-568
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Palmitic acid induces interleukin-1β secretion via NLRP3 inflammasomes and inflammatory responses through ROS production in human placental cells. (2016)
  • Author(s): Shirasuna K, Takano H, Seno K, Ohtsu A, Karasawa T, Takahashi M, Ohkuchi A, Suzuki H, Matsubara S, Iwata H, Kuwayama T.
  • Journal Title: J Reprod Immunol Volume: 116 Pages: 104-112
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Moderate Hypoxia Down-Regulates Interleukin-6 Secretion and TLR4 Expression in Human Sw.71 Placental Cells. (2015)
  • Author(s): Shirasuna K, Shimamura N, Seno K, Ohtsu A, Shiratsuki S, Ohkuchi A, Suzuki H, Matsubara S, Nagayama S, Iwata H, Kuwayama T.
  • Journal Title: Cell Physiol Biochem Volume: 36 Issue: 6 Pages: 2149-2160
  • DOI: 10.1159/000430181
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Advanced Glycation End Products (AGE)はヒトおよびマウス胎盤でinterleukin-1b産生を調節する (2017)
  • Author(s): 1)白砂孔明，妹尾琴実，高橋宏典，大口昭英，鈴木寛正，岩田尚孝，桑山岳人
  • Organizer: 第25回日本胎盤学会