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Role of matrix met alloprot einases and cytokines in the development of endometriosis

Research Project

Project/Area Number 14370534
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionTottori University School of Medicine

Principal Investigator

TERAKAWA Naoki  Tottori Univ., Dept.Obst et.Gynecol., Professor, 医学部, 教授 (90163906)

Co-Investigator(Kenkyū-buntansha) TANIGUCHI Fuminori  Tottori Univ., Dept.Obst et.Gynecol., Research Associates, 医学部附属病院, 助手 (40322218)
IWABE Tomio  Tottori Univ., Dept.Obst et.Gynecol., Assistant Professor, 医学部附属病院, 講師 (10284001)
HARADA Tasuku  Tottori Univ., Dept.Obst et.Gynecol., Assistant Professor, 医学部, 講師 (40218649)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
KeywordsEndometriosis / Development and progression / Endometriotic stromal cells / Cytokine TNFα / IL-8 / Nuclear fact or-κB / Estrogen / GnRH agonist / 間質細胞 / 発生・進展 / サイトカインファミリー / TNF-α / 遺伝子発現
Research Abstract

It is believed that the extracellular matrix (ECM) remodeling is relevant to the development and the progression of endometriosis. Tissue remodeling involving ECM turnover is regulated by the combined action of matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs). It has been reported that the concentration of MMP-1 is increased and that of TIMP-1 is decreased in peritoneal fluid of patients with endometriosis. The present study was undertaken to investigate the possible role of MMPs and TIMPs in the development of endometriosis. In this study, however, we did not find any difference in the levels of MMP-1 and TIMP-1 in peritoneal fluid between infertile patients with and without endometriosis.
We previously reported that TNF a promoted proliferation of endometriotic stromal cells by inducing IL-8 gene and protein expression. We hypothesize that TNF a may induce IL-S production in endometriotic cells through nuclear factor-κB (NF-κB) activation. Western blot analyses and EMSA revealed that incubation with TNF α induced the expression of p-I κB and activation of NF-κB in endometriotic stromal cells. The addition of TNF α (0.1ng/ml) significantly increased protein and gene expression of IL-8 in the cells of patients without GnRH agonist treatment, but this expression was not observed in the cells of patients with GnRHa. The addition of E2 (10^<-7>M) enhanced the expression of IL-8. However, in the cells of patients who received GnRHa treatment, TNF α and E2 did not show any significant effect. These findings demonstrate that NF-κ B activation is critical for TNF α-induced IL-8 expression in endometriotic stromal cells. The current study showed for the first time that GnRHa treatment attenuated the expression of IL-8 by reducing TNF α-induced NF-κB activation.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] A.Fujii: "Interleukin-8 gene and protein expression are up-regulated by interleukin-1β in normal human ovarian cells and a granulosa tumor cell line"Fertil.Steril.. 79. 151-157 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Sakamoto: "Tumor necrosis factor-α-induced interleukin-8 (IL-8) expression in endometriotic stromal cells, probably through nuclear factor-κB activation : gonadotropin-releasing hormone agonist treatment reduced IL-8 expression"J.Clin.Endocrinol.Metab.. 88. 730-735 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] F.Taniguchi: "Activation of mitogen-activated protein kinase pathway by keratinocyte growth factor or fibroblast growth factor-10 promotes cell proliferation in human endometrial carcinoma cells"J.Clin.Endocrinol.Metab.. 88. 773-780 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Iwabe: "Gonadotropin-releasing hormone agonist treatment reduced serum interleukin-6 concentrations in patients with ovarian endometriomas"Fertil.Steril.. 80. 300-304 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] N.Terakawa: "Loss of PTEN expression followed by Akt phosphorylationis a poor prognosticfactor for patients with endometrial cancer"Endocr.Relat.Cancer. 10. 203-208 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Tagashira: "Ovarian endometrioid adenocarcinoma arising from endometriosis in a young woman"Gynecol.Oncol.. 91. 643-647 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Harada: "Apoptosis in human endometrium and endometriosis"Hum.Reprod.Update. 10. 29-38 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Yoshida: "Hepatocyte growth factor/Met system promotes endometrial and endometriotic stromal cell invasion via autocrine and paracrine pathways"J.Clin.Endocrinol.Metab.. 89. 823-832 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] A.Fujii: "Interleukin-8 gene and protein expression are up-regulated by interleukin-1β in normal human ovarian cells and a granulosa tumor cell line"Fertil.Steril.. 79(2). 151-157 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Sakamoto: "Tumor necrosis factor-α-induced interleukin-8 (IL-8) expression in endometriotic stromal cells, probably through nuclear factor-κB activation : gonadotropin-releasing hormoneagonist treatment reduced IL-8 expression"J.Clin.Endocrinol.Metab.. 88(2). 730-735 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] F.Taniguchi: "Activation of mitogen-activated protein kinase pathway by keratinocytegrowth factor or fibroblast growth factor-10 promotes cell proliferation in human endometrial carcinoma cells"J.Clin.Endocrinol.Metab.. 88(2). 773-780 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Iwabe: "Gonadotropin-releasing hormone agonist treatment reduced serum interleukin-6 concentrations in patients with ovarian endometriomas"Fertil.Steril.. 80(2). 300-304 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] N.Terakawa: "Loss of PTEN expression followed by Akt phosphorylation is a poor prognostic factor for patients with endometrial cancer"Endocr.Relat.Cancer. 10(2). 203-208 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Tagashira: "Ovarian endometrioid adenocarcinoma arising from endometriosis in a young woman"Gynecol.Oncol.. 91(3). 643-647 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Harada: "Apoptosis in human endometrium and endometriosis"Hum.Reprod.Update. 10(1). 29-38 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Yoshida: "Hepatocyte growth factor/Met system promotes endometria and endometriotic stromal cell invasion via autocrine and paracrine pathways"J.Clin.Endocrinol.Metab.. 89(2). 823-832 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Iwabe: "Gonadotropin-releasing hormone agonist treatment reduced serum interleukin-6 concentrations in patients with ovarian endometriomas"Fertil.Steril.. 80・2. 300-304 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] N.Terakawa: "Loss of PTEN expression followed by Akt phosphorylation is a poor prognostic factor for patients with endometrial cancer"Endocr.Relat.Cancer. 10・2. 203-208 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Y.Tagashira: "Ovarian endometrioid adenocarcmoma arising from endometriosis in a young woman"Gynecol.Oncol.. 91・3. 643-647 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.Harada: "Apoptosis in human endometrium and endometriosis"Hum.Reprod.Update. 10・1. 29-38 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] S.Yoshida: "Hepatocyte growth factor/Met system promotes endometrial and endometriotic stromal cell invasion via autocrine and paracrine pathways"J.Clin.Endocrinol.Metab.. 89・2. 823-832 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] A.Fujii: "Interleukin-8 gene and protein expression are up-regulated by interleukin-1β in normal human ovarian cells and a granulosa tumor cell line"Fertil. Steril.. 79・1. 151-157 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Sakamoto: "Tumor necrosis factor-α-induced interleukin-8 (IL-8) expression in endometriotic stromal cells, probably through nuclear factor-κ B activation : gonadotropin-releasing hormone agonist treatment reduced IL-8 expression"J. Clin. Endocrinol. Metab.. 88・2. 730-735 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] F.Taniguchi: "Activation of mitogen-activated protein kinase pathway by keratinocyte growth factor or fibroblast growth factor-10 promotes cell proliferation in human endometrial carcinoma cells"J. Clin. Endocrinol. Metab.. 88・2. 773-780 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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