| Project/Area Number |
12470350
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
KANZAKI Hideharu Kansai Medical University, Faculty of Medicine, Professor, 医学部, 教授 (80135566)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Atsuya Kansai Medical University, Faculty of Medicine, Instructor, 医学部, 助手 (00268351)
SAITO Junko Kansai Medical University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (00205650)
YASUDA Katsuhiko Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (90174507)
OKADA Hidetaka Kansai Medical University, Faculty of Medicine, Instructor, 医学部, 助手 (80330182)
松原 高史 関西医科大学, 医学部, 助手 (50229522)
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| Project Period (FY) |
2000 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥10,900,000 (Direct Cost: ¥10,900,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | human endometrium / NK cells / dendritic cells / hCG / IL-15 / progesterone / 20α-HSD / 子宮内膜 / 局所免疫 / fibrin / IL-1 / 妊娠 / 着床障害 / 胎盤 / サイトカイン / 性ステロイドホルモン / 不妊 / 分化関連遺伝子 / 増殖因子 / 免疫細胞 |
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| Research Abstract |
In human endometrium, cytokines and immune cells play very important role(s) for endometrial cell proliferation and differentiation required for implantation. In addition, these are indispensable factors for the maintenance of pregnancy. And It has been suggested that endometrial natural killer(NK) cells and endometrial dendritic cells(DOs) play key roles in the regulation of endometrial immune system. By using human cDNA expression array, human IL-15 gene was identified as an up-regulated transcriptional product during the secretory phase endometrium in comparison with the proliferative one. In vitro decidualization system with human endometrial stromal cells, it was demonstrated that the expression of IL-15 mRNA is up-regulated by progesterone not by estrogen. But the production of IL-15 during the culture was enhanced by the addition of estrogen. Since endometrial NK cells have receptors for IL-15 and proliferated by rIL-15 in vitro, IL-15 is believed to be a mediator of progesterone action in human endometrium. During pregnancy, myeloid DCs increased in the late stage, while lymphoid DCs decreased gradually. The addition of hCG to cultures significantly induced the maturation of both DC subsets, and hCG receptor was found in both subsets, indicating that endometrial immune systems are modulated by hCG as well as progesterone. Further analysis with microarray system revealed the progesterone-induced genes of IL-1 receptor type 1, fiburin-1,fiburin-2,microsomal glutathione S-transferase 1,fumarylacetoacetate hydrolase and orphan G protein-coupled receptor. We confirmed the in vitro as well in vivo gene expression of fiburins and found that the fiburins are indispensable mediator for progesterone action in human endometrial decidualization.
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