2010 Fiscal Year Final Research Report
The role of immune cells in endometriosis
Project/Area Number |
20591908
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Obstetrics and gynecology
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Research Institution | The University of Tokyo |
Principal Investigator |
OSUGA Yutaka 東京大学, 医学部・附属病院, 准教授 (80260496)
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Project Period (FY) |
2008 – 2010
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Keywords | 子宮内膜症 / 免疫 / 炎症 |
Research Abstract |
(1) In a novel paradigm of T cell differentiation, type 17 T helper(Th17) cells may play a significant role in endometriosis, a chronic inflammatory disease. Our findings suggested that the CCL20/CCR6 system is involved in the migration of Th17 cells to endometriotic tissues and that proinflammatory cytokines contribute to the development of endometriosis via up-regulation of CCL20 secretion from endometriotic stromal cells.(2) Proteinase-activated receptor 2(PAR2) is a G-protein-coupled receptor that is activated by several serine proteases. PAR2 activation in endometriotic stromal cells(ESCs) has been implicated in the development of endometriosis but the regulatory mechanism of PAR2 expression in ESC is unknown. In view of significant roles of PAR2 and IL-6 in endometriosis, our finding that TGF-β1 induced increase in PAR2 expression in ESC may be an elaborate mechanism that augments the progression of the disease.(3) IL-17F increased the secretion of IL-8 from ESCs, and the effect was inhibited by antibodies for IL-17 receptor A and IL-17 receptor C. Tumor necrosis factorα(TNF-α) synergistically enhanced IL-17F-induced increase in IL-8 secretion from ESCs. The IL-17F increased the gene expression of IL-8 and COX2 in ESCs. These findings suggest that IL-17F may stimulate the development of endometriosis by up-regulation of IL-8 and COX2.(4) Inflammatory stimuli, interleukin(IL)-1β, and tumor necrosis factor(TNF)-αinduced inhibin/activin-βA subunit mRNA and activin-A protein expression in EoSC. Additionally, activin-A enhanced EoSC proliferation and increased the expression of IL-6 and protease-activated receptor(PAR)-2 mRNA. An in vitro study revealed that activin-A, which is induced by IL-1βor TNF-α, might promote endometriosis by stimulating IL-6 and PAR-2 mRNA expression and increasing the proliferation of EoSC.
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Research Products
(67 results)
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[Journal Article] Dienogest, a new conservative strategy for extragenital endometriosis : a pilot study2011
Author(s)
Harada M., Osuga Y., Izumi G., Takamura M., Takemura Y., Hirata T., Yoshino O., Koga K., Yano T., Taketani Y.
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Journal Title
Gynecol Endocrinol
Volume: 27
Pages: 717-20
Peer Reviewed
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[Journal Article] High mobility group box 1(HMGB1) levels in the placenta and in serum in preeclampsia2011
Author(s)
Wang B., Koga K., Osuga Y., Hirata T., Saito A., Yoshino O., Hirota Y., Harada M., Takemura Y., Fujii T., Taketani Y.
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Journal Title
Am J Reprod Immunol
Volume: 66
Pages: 143-148
Peer Reviewed
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[Journal Article] Toll-like receptor-3 ligation-induced indoleamine 2, 3-dioxygenase expression in human trophoblasts2011
Author(s)
Wang B., Koga K., Osuga Y., Cardenas I., Izumi G., Takamura M., Hirata T., Yoshino O., Hirota Y., Harada M., Mor G., Taketani Y.
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Journal Title
Endocrinology
Volume: 152
Pages: 4984-4992
Peer Reviewed
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[Journal Article] GF-beta1 induces proteinase-activated receptor 2(PAR2) expression in endometriotic stromal cells and stimulates PAR2 activation-induced secretion of IL-62011
Author(s)
Saito A., Osuga Y., Yoshino O., Takamura M., Hirata T., Hirota Y., Koga K., Harada M., Takemura Y., Yano T., Taketani Y.
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Journal Title
Hum Reprod
Volume: 26
Pages: 1892-1898
Peer Reviewed
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[Journal Article] Decreased pregnancy rate is linked to abnormal uterine peristalsis caused by intramural fibroids2010
Author(s)
Yoshino O., Hayashi T., Osuga Y., Orisaka M., Asada H., Okuda S., Hori M., Furuya M., Onuki H., Sadoshima Y., Hiroi H., Fujiwara T., Kotsuji F., Yoshimura Y., Nishii O., Taketani Y.
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Journal Title
Hum Reprod
Volume: 25
Pages: 2475-2479
Peer Reviewed
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[Journal Article] Progesterone decreases bone morphogenetic protein(BMP) 7 expression and BMP7 inhibits decidualization and proliferation in endometrial stromal cells2010
Author(s)
Kodama A, Yoshino O, Osuga Y, Harada M, Hasegawa A, Hamasaki K, Takamura M, Koga K, Hirota Y, Hirata T, Takemura Y, Yano T, Taketani Y
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Journal Title
Hum Reprod
Volume: 25
Pages: 751-756
Peer Reviewed
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[Journal Article] Uterine FK506-binding protein 52(FKBP52)-peroxiredoxin-6(PRDX6) signaling protects pregnancy from overt oxidative stress2010
Author(s)
Hirota Y., Acar N., Tranguch S., Burnum K. E., Xie H., Kodama A., Osuga Y., Ustunel I., Friedman D. B., Caprioli R. M., Daikoku T., Dey S. K.
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Journal Title
Proc Natl Acad Sci U S A
Volume: 107
Pages: 15577-15582
Peer Reviewed
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[Journal Article] Recruitment of CCR6-expressing Th17 cells by CCL 20 secreted from IL-1 beta-, TNF-alpha-, and IL-17A-stimulated endometriotic stromal cells2010
Author(s)
Hirata T., Osuga Y., Takamura M., Kodama A., Hirota Y., Koga K., Yoshino O., Harada M., Takemura Y., Yano T., Taketani Y.
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Journal Title
Endocrinology
Volume: 151
Pages: 5468-5476
Peer Reviewed
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[Journal Article] Bone morphogenetic protein-6 stimulates gene expression of follicle-stimulating hormone receptor, inhibin/activin beta subunits, and anti-Mullerian hormone in human granulosa cells2009
Author(s)
Shi J, Yoshino O, Osuga Y, Koga K, Hirota Y, Hirata T, Yano T, Nishii O, Taketani Y
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Journal Title
Fertil Steril
Volume: 92
Pages: 1794-1798
Peer Reviewed
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[Presentation] 筋層内子宮筋腫(intramural myoma : IM)により誘導される子宮内膜の異常蠕動は妊娠率を低下させる2011
Author(s)
吉野修,浅田弘法,折坂誠,大須賀穣,土屋裕子,佐渡島陽子,古谷正敬,小辻文和,吉村泰典,西井修,武谷雄二
Organizer
第63回産科婦人科学会
Place of Presentation
大阪市
Year and Date
2011-08-29
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[Presentation] 子宮内膜症進展におけるIL-17、GRO(Growth Related Oncogene)αを介したvicious cycleの形成2011
Author(s)
高村将司,大須賀穣,泉玄太郎,齊藤亜子,長谷川亜希子,竹村由里,原田美由紀,平田哲也,広田泰,吉野修,甲賀かをり,武谷雄二
Organizer
第63回産科婦人科学会
Place of Presentation
大阪市
Year and Date
2011-08-29
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[Presentation]2011
Author(s)
泉玄太郎,甲賀かをり,大須賀穣,永井美和子,浦田陽子,高村将司,齊藤亜子,竹村由里,原田美由紀,吉野修,矢野哲,武谷雄二
Organizer
第63回産科婦人科学会
Place of Presentation
大阪市
Year and Date
2011-08-29
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[Presentation] 鎌状赤血球症合併妊娠の一例2010
Author(s)
大橋奈尾子,嘉本寛江,永松健,吉田志朗,兵藤博信,大知行,上妻志郎,武谷雄二
Organizer
第120回日本産科婦人科学会関東連合地方部会
Place of Presentation
つくば市
Year and Date
2010-11-28
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[Presentation] 妊娠後期に合失調症が増悪し,電気けいれん療法で改善を認め満期産に至った一例2010
Author(s)
神尊貴裕,北麻里子,兵藤博信,小松篤史,吉田志朗,大須賀穣,亀井良政,藤井知之,上妻志朗,武谷雄二
Organizer
第120回日本産科婦人科学会関東連合地方部会
Place of Presentation
つくば市
Year and Date
2010-11-28
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[Presentation] 卵管采原発の卵管症の1例2010
Author(s)
井上恵莉,土屋聡,織田克利,川名敬,中川俊介,大須賀穣,百枝幹雄,矢野哲,武谷雄二
Organizer
第120回日本産科婦人科学会関東連合地方部会
Place of Presentation
つくば市
Year and Date
2010-11-28
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[Presentation] 子宮腺筋症に対するDienogestの効果2010
Author(s)
泉玄太郎,平田哲也,甲賀かをり,大須賀穣,高村将司,小倉さやか,児玉亜北麻里子,竹村由里,森本千恵子,矢野哲,武谷雄二
Organizer
第62回日本産科婦人科学会
Place of Presentation
東京
Year and Date
2010-04-24
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[Presentation] TGFβは子宮内膜症細胞においてPAR2の発現・機能を促進する2009
Author(s)
児玉亜子,大須賀穣,吉野修,泉玄太郎高村将司,長谷川亜希子,竹村由里,原田美由紀,平田哲也,広田泰,甲賀かをり,矢野哲,武谷雄二
Organizer
第14回生殖内分泌学会
Place of Presentation
東京
Year and Date
2009-11-28
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[Presentation] ART妊娠と一般不妊妊娠の周産期予後の検討2009
Author(s)
堤亮,藤本晃久,竹村由里,小泉美奈子,渡辺裕子,大井なぎさ,田中慧,張士青,廣井久彦,大須賀穣,矢野哲,武谷雄二
Organizer
第54回日本生殖医学会
Place of Presentation
金沢
Year and Date
2009-11-22
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[Presentation] 低用量ピルは腹腔鏡下子宮内膜症性卵巣嚢胞摘出術の術後再発を低下させる2009
Author(s)
崎かほり,田島敏樹,長谷川亜希子,竹村由里,原田美由紀,森本千恵子,平田哲也,廣田泰,吉野修,大須賀穣,武谷雄二
Organizer
第54回日本生殖医学会
Place of Presentation
金沢
Year and Date
2009-11-22
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[Presentation] 診断的腹腔鏡検査で左付属器欠損と腹腔内遊離体を発見した一例2009
Author(s)
永井美和子,甲賀かをり,平田哲也,平池修,藤本晃久,廣井久彦,大須賀穣,矢野哲,上妻志郎,武谷雄二,福嶋敬宜
Organizer
第117回日本産科婦人科学会関東連合地方部会
Place of Presentation
東京
Year and Date
2009-06-14
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[Presentation] Tunicamycin(TM)は子宮内膜症間質細胞におけるTRAIL誘導性アポトーシスを特異的に増強する2009
Author(s)
長谷川亜希子,大須賀穣,広田泰,濱崎かほり,児玉亜子,原田美由紀,竹村由里,平田哲也,森本千恵子,吉野修,矢野哲,武谷雄二
Organizer
第61回日本産科婦人科学会
Place of Presentation
京都
Year and Date
2009-04-03
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