Allergic inflammation in the development of endometriosis

• Project/Area Number: 23592395
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: The University of Tokyo
• Principal Investigator: YUTAKA Osuga 東京大学, 医学部附属病院, 教授 (80260496)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: アレルギー / 免疫 / 子宮内膜症 / 炎症 / Th2免疫 / トリプトファン代謝

Research Abstract

Endometriosis is a chronic inflammatory disease in which the Th2 immune response is activated and has been suggested to promote the disease. TSLP is a master cytokine that drive Th2 immune response.
IL-1b stimulated the expression of TSLP mRNA and secretion of TSLP protein from ESCs. IL-4 enhanced the IL-1b-induced TSLP secretion from ESCs, while IFNg reduced it. Inhibitors of p42/44 MAPK, p38 MAPK and SAPK/JNK suppressed the IL-1b-induced secretion of TSLP from ESCs. Positive immunostaining of TSLP was observed in the stroma of endometrioma tissue. TSLP concentrations in the serum and PF were both higher in women with endometriosis compared with those without endometriosis.
This study provided new insights in the Th2 immune response-related mechanism in endometriosis.

Research Products

• [Journal Article] Resveratrol suppresses inflammatory responses in endometrial stromal cells derived from endometriosis: A possible role of the sirtuin 1 pathway (2014)
  • Author(s): Taguchi A, Wada-Hiraike O, Kawana K, Koga K, Yamashita A, Shirane A, Urata Y, Kozuma S, Osuga Y, Fujii T
  • Journal Title: J Obstet Gynaecol Res Volume: 40 Issue: 3 Pages: 770-8
  • DOI: 10.1111/jog.12252
  • Peer Reviewed
• [Journal Article] Individualized management of umbilical endometriosis: a report of seven cases (2014)
  • Author(s): Saito A, Koga K, Osuga Y, Harada M, Takemura Y, Yoshimura K, Yano T, Kozuma S
  • Journal Title: J Obstet Gynaecol Res Volume: 40 Issue: 1 Pages: 40-5
  • DOI: 10.1111/jog.12118
  • Peer Reviewed
• [Journal Article] Factors that predict poor clinical course among patients hospitalized with pelvic inflammatory disease (2013)
  • Author(s): Terao M, Koga K, Fujimoto A, Wada-Hiraike O, Osuga Y, Yano T, Kozuma S
  • Journal Title: J Obstet Gynaecol Res Volume: 40 Issue: 2 Pages: 495
  • DOI: 10.1111/jog.12189
  • Peer Reviewed
• [Journal Article] Burden of menstrual symptoms in Japanese women - an analysis of medical care-seeking behavior from a survey-based study (2013)
  • Author(s): Tanaka E, Momoeda M, Osuga Y, Rossi B, Nomoto K, Hayakawa M, Kokubo K, Wang EC
  • Journal Title: Int J Womens Health Volume: 6 Pages: 11-23
  • DOI: 10.2147/ijwh.s52429
  • Peer Reviewed
• [Journal Article] Omega-3 Polyunsaturated Fatty Acids Suppress the Cystic Lesion Formation of Peritoneal Endometriosis in Transgenic Mouse Models (2013)
  • Author(s): Tomio K, Kawana K, Taguchi A, Isobe Y, Iwamoto R, Yamashita A, Kojima S, Mori M, Nagamatsu T, Arimoto T, Oda K, Osuga Y, Taketani Y, Kang JX, Arai H, Arita M, Kozuma S, Fujii T.
  • Journal Title: PLoS One Volume: 8 Issue: 9 Pages: 2013-2013
  • DOI: 10.1371/journal.pone.0073085
  • Peer Reviewed
• [Journal Article] Interleukin-4 and prostaglandin E2 synergistically up-regulate 3β-hydroxysteroid dehydrogenase type 2 in endometrioma stromal cells (2013)
  • Author(s): Urata Y, Osuga Y, Akiyama I, Nagai M, Izumi G, Takamura M, Hasegawa A, Harada M, Hirata T, Hirota Y, Yoshino O, Koga K, Kozuma S
  • Journal Title: J Clin Endocrinol Metab Volume: 98(4) Issue: 4 Pages: 1583-90
  • DOI: 10.1210/jc.2012-3475
  • Peer Reviewed
• [Journal Article] Follistatin is induced by IL-1βand TNF-αin stromal cells from endometrioma (2013)
  • Author(s): Akiyama I, Yoshino O, Osuga Y, Izumi G, Urata Y, Hirota Y, Hirata T, Harada M, Koga K, Ogawa K, Kozuma S
  • Journal Title: Reprod Sci Volume: 20(6) Issue: 6 Pages: 675-9
  • DOI: 10.1177/1933719112463253
  • Peer Reviewed
• [Journal Article] Increased risk of placenta previa is associated with endometriosis and tubal factor infertility in assisted reproductive technology pregnancy (2013)
  • Author(s): Takemura;Osuga;Fujimoto;Oi;Tsutsumi;Koizumi;Harada;Yano;Taketani .
  • Journal Title: Gynecological Endocrinology Volume: 29 Issue: 2 Pages: 113
  • DOI: 10.3109/09513590.2012.706669
  • Peer Reviewed
• [Journal Article] 内分泌ホルモンのすべて (2013)
  • Author(s): 大須賀穣
  • Journal Title: (第10章)性ホルモン関連エストロゲン・プロゲステロン.内分泌・糖尿病・代謝内科(1884-2917) Volume: 36巻Suppl Pages: 345-351
• [Journal Article] エキスパートの子宮内膜症・子宮腺筋症治療 (2013)
  • Author(s): 大須賀穣
  • Journal Title: 手術療法チョコレート嚢胞産婦人科の実際(0558-4728) Volume: 62巻5号 Pages: 651-657
• [Journal Article] Interleukin-17A is present in neutrophils in endometrioma and stimulates the secretion of growth-regulated oncogene-α (Gro-α) from endometrioma stromal cells (2012)
  • Author(s): Takamura M, Osuga Y, Izumi G, Yoshino O, Koga K, Saito A, Hirata T, Hirota Y, Harada M, Hasegawa A, Taketani Y
  • Journal Title: Fertil Steril Volume: 98 Issue: 5 Pages: 1218-24
  • DOI: 10.1016/j.fertnstert.2012.07.1117
  • Peer Reviewed
• [Journal Article] Urata Y, Osuga Y, Izumi G, Takamura M, Koga K, Nagai M, Harada M, Hirata T, Hirota Y, Yoshino O, Taketani Y (2012)
  • Author(s): Interleukin-1β stimulates the secretion of thymic stromal lymphopoietin (TSLP) from endometrioma stromal cells: possible involvement of TSLP in endometriosis.
  • Journal Title: Hum Reprod Volume: 27 Issue: 10 Pages: 3028-35
  • DOI: 10.1093/humrep/des291
  • Peer Reviewed
• [Journal Article] Proteinase-activated receptors in the endometrium and endometriosis (2012)
  • Author(s): Osuga Y, Hirota Y, Yoshino O, Hirata T, Koga K, Taketani Y
  • Journal Title: Front Biosci (Schol Ed) Volume: Review Pages: 1201-12
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22652866
  • Peer Reviewed
• [Journal Article] Diameter of dominant leiomyoma is a possible determinant to predict coexistent endometriosis (2012)
  • Author(s): Isono W, Wada-Hiraike O, Osuga Y, Yano T, Taketani Y
  • Journal Title: Eur J Obstet Gynecol Reprod Biol Volume: 162(1) Issue: 1 Pages: 87-90
  • DOI: 10.1016/j.ejogrb.2012.01.018
  • Peer Reviewed
• [Journal Article] 子宮内膜症・子宮腺筋症-最近の話題- (2012)
  • Author(s): 大須賀穣
  • Journal Title: 子宮内膜症子宮内膜症の病態の新たな側面. HORMONE FRONTIER IN GYNECOLOGY Volume: 19巻4号 Pages: 291-296
• [Journal Article] 子宮内膜症の病因・病態をめぐって内分泌学的・免疫学的アプローチから (2012)
  • Author(s): 大須賀穣
  • Journal Title: 日本産科婦人科学会雑誌 Volume: 64巻1号 Pages: 105-111
  • NAID: 110008913810
• [Journal Article] Activin-A is induced by interleukin-1β and tumor necrosis factor-α and enhances the mRNA expression of interleukin-6 and protease-activated receptor-2 and proliferation of stromal cells from endometrioma (2011)
  • Author(s): Yoshino O, Izumi G, Shi J, Osuga Y, Hirota Y, Hirata T, Harada M, Nishii O, Koga K, Taketani Y
  • Journal Title: Fertil Steril Volume: 96 Issue: 1 Pages: 118
  • DOI: 10.1016/j.fertnstert.2011.05.006
  • Peer Reviewed
• [Journal Article] Interleukin-17F increases the secretion of interleukin-8 and the expression of cyclooxygenase 2 in endometriosis (2011)
  • Author(s): Hirata T, Osuga Y, Takamura M, Saito A, Hasegawa A, Koga K, Yoshino O, Hirota Y, Harada M, Taketani Y
  • Journal Title: Fertil Steril Volume: 96(1) Issue: 1 Pages: 113-7
  • DOI: 10.1016/j.fertnstert.2011.04.060
  • Peer Reviewed
• [Journal Article] TGF-β1 induces proteinase-activated receptor 2 (PAR2) expression in endometriotic stromal cells and stimulates PAR2 activation-induced secretion of IL-6 (2011)
  • Author(s): Saito A, Osuga Y, Yoshino O, Takamura M, Hirata T, Hirota Y, Koga K, Harada M, Takemura Y, Yano T, Taketani Y
  • Journal Title: Hum Reprod Volume: 26(7) Issue: 7 Pages: 1892-8
  • DOI: 10.1093/humrep/der125
  • Peer Reviewed
• [Journal Article] Dienogest, a new conservative strategy for extragenital endometriosis : a pilot study (2011)
  • Author(s): Harada M, Osuga Y, Izumi G, Takamura M, Takemura Y, Hirata T, Yoshino O, Koga K, Yano T, Taketani Y
  • Journal Title: Gynecol Endocrinol Volume: 27(9) Issue: 9 Pages: 717-20
  • DOI: 10.3109/09513590.2010.533800
  • Peer Reviewed
• [Journal Article] Interleukin-17F increases the secretion of interleukin-8 and the expression of cyclooxygenase 2 in endometriosis (2011)
  • Author(s): Hirata T, Osuga Y, Takamura M, Saito A, Hasegawa A, Koga K, Yoshino O, Hirota Y, Harada M, Taketani Y.
  • Journal Title: Fertil Steril Volume: 96 Pages: 113-117
  • Peer Reviewed
• [Presentation] 子宮内膜症の病態解明最前線 (2014)
  • Author(s): 大須賀穣
  • Organizer: 日本エンドメトリオーシス学会
  • Place of Presentation: 鹿児島、城山観光ホテル
  • Invited
• [Presentation] 子宮内膜症間質細胞においてIL-4とPGE2は3beta hydroxysteroid dehydrogenase type 2 (HSD3B2)を相乗的に誘導する (2013)
  • Author(s): 浦田陽子、大須賀穣、秋山育美、永井美和子、泉玄太郎、高村将司、長谷川亜希子、原田美由紀、平田哲、廣田泰、吉野修、甲賀かをり、藤井知行
  • Organizer: 第58回日本生殖医学会学術講演会
  • Place of Presentation: 神戸
  • Year and Date: 2013-11-15
• [Presentation] INTERLEUKIN-1beta INCREASES EXPRESSION OF TRYPTOPHAN 2,3-DIOXYGENASE AND STIMULATES TRYPTOPHAN (2013)
  • Author(s): Urata Y, Osuga Y, Koga K, Hirota Y, Hirata T, Fuji T
  • Organizer: A conjoint meeting of the International Federation of Fertility Societies and the American Society for Reproductive
  • Place of Presentation: ボストン
  • Year and Date: 2013-10-14
• [Presentation] Interleukin (IL)-4 and prostaglandin (PG) E2 synergistically increase the expression of 3beta hydroxysteroid dehydrogenase type 2 (HSD3B2) in endometrioma stromal cells (2013)
  • Author(s): Urata Y, Osuga Y, Nagai M, Izumi G, Takamura M, Harada M, Hirata T, Hirota Y, Yoshino O, Koga K, Yano T, Kozuma S
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: 札幌
  • Year and Date: 2013-05-10
• [Presentation] IL-1βは子宮内膜症細胞のTDO発現増加を介してトリプトファン代謝を亢進する (2013)
  • Author(s): 浦田陽子、大須賀穣、秋山育美、中澤明里、宮下真理子、原口広史、永井美和子、泉玄太郎、山本直子、原田美由紀、平田哲也、廣田泰、吉野修、甲賀かをり、上妻志郎
  • Organizer: 第32回日本エンドメトリオーシス学会
  • Place of Presentation: 栃木
  • Year and Date: 2013-01-18
• [Presentation] 子宮内膜症間質細胞においてIL-4とPGE2は3beta hydroxysteroid dehydrogenase type 2(HSD3B2)を相乗的に誘導する (2013)
  • Author(s): 浦田 陽子, 大須賀 穣, 秋山 育美, 永井 美和子, 泉 玄太郎, 高村 将司, 長谷川 亜希子, 原田 美由紀, 平田 哲, 廣田 泰, 吉野 修, 甲賀 かをり, 藤井 知行
  • Organizer: 日本生殖医学会
  • Place of Presentation: 神戸、ポートピアホテル
• [Presentation] Y Interleukin-4 and prostaglandin E2 synergistically upregulate 3beta-hydroxysteroid dehydrogenase type 2 in endometrioma stromal cells (2012)
  • Author(s): Urata Y, Osuga, Y, Izumi, G, Nagai, M, Takamura, M, Yamamoto, N, Saito, A, Hasegawa, A, Takemura, Y, Harada, M, Hirata, T, Hirota, Y, Yoshino, O, Koga, K, Taketani
  • Organizer: European Society of Human Reproduction and Embryology
  • Place of Presentation: イスタンブール
  • Year and Date: 2012-07-01
• [Presentation] 子宮内膜症におけるthymic stromal lymphopoietinの発現制御とその意義 (2012)
  • Author(s): 浦田陽子、大須賀穣、永井美和子、泉玄太郎、高村将司、長谷川亜希子、原田美由紀、廣田泰、吉野修、甲賀かをり、矢野哲、武谷雄二
  • Organizer: 第64回日本産科婦人科学会学術講演会
  • Place of Presentation: 神戸
  • Year and Date: 2012-04-15
• [Presentation] IL-17Aは子宮内膜症細胞のトリプトファンジオキシゲナーゼ発現を増加させる (2012)
  • Author(s): 浦田陽子、大須賀穣、永井美和子、泉玄太郎、山本直子、高村将司、齊藤亜子、長谷川亜希子、原田美由紀、森本千恵子、平田哲也、吉野修、甲賀かをり、武谷雄二
  • Organizer: 第31回日本エンドメトリオーシス学会
  • Place of Presentation: 長崎
  • Year and Date: 2012-01-21
• [Book] 子宮内膜症と生殖、産婦人科学レビュー (2011)
  • Author(s): 大須賀穣
  • Publisher: 総合医学社
• [Book] 序文:子宮腺筋症・子宮内膜症における最近の動向 (2011)
  • Author(s): 大須賀穣
  • Publisher: 日本臨床社
• [Book] 子宮腺筋症総論、:子宮腺筋症・子宮内膜症における最近の動向 (2011)
  • Author(s): 大須賀穣
  • Publisher: 日本臨床社
• [Remarks]
  • URL: http://square.umin.ac.jp/tkyobgyn/