| 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 |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | The University of Tokyo |
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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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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 子宮内膜症 / 免疫 / 炎症 / Th17細胞 / IL-17 / ケモカイン / TGF-β / proteinase-activated receptor 2 / interleukin-6 / Th17 / CCR6 / CCL20 |
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| 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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