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Role of cytokines in development of endometriosis

Research Project

Project/Area Number 10671540
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

HARADA Tasuku  Tottori Univ., Sch. of Med., Obstetrics and Gynecology, Associated Professor, 医学部, 講師 (40218649)

Co-Investigator(Kenkyū-buntansha) IWABE Tomio  Tottori Univ., Sch. of Med., Obstetrics and Gynecology, Assistant, 医学部・附属病院, 助手 (10284001)
TERAKAWA Naoki  Tottori Univ., Sch. of Med., Obstetrics and Gynecology, Professor, 医学部, 教授 (90163906)
谷川 正浩  鳥取大学, 医学部・附属病院, 助手 (90236688)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsendometriosis / cytokine / MMP / TIMP / interleukin-6 / interleukin-10 / endometrium / IL-6 soluble receptor / インターロイキンー6 / インターロイキンー10 / ILー6可溶性受容体
Research Abstract

We have measured peritoneal fluid (PF) levels of matrix metalloproteinase-9 (MMP-9), its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-10 (IL-10) in patients with endometriosis. Although the concentrations of MMP-9 was below the detectable level, high concentrations of TIMP-1 and IL-10 were present in the PF. The levels of IL-10 in PF was significantly higher in patients with endometriosis than in patients without endometriosis. In order to examine the effects of IL-6 or IL-10 on the gene expression of TIMP-1, endometrial and endometriotic stromal cells were collected from the uterus or from ovarian chocolate cysts. The stimulatory effects of these cytokines have been elucidated.
We have conducted the study to investigate the possible role of IL-6, soluble IL-6 receptor in the growth of endometrial and endometriotic cells. We examined the effect of IL-6, soluble IL-6 receptor or combination of both factors on the proliferation of endometrial and endometriot … More ic stromal cells. IL-6 receptor had no effect on the growth of stromal cells in tissue from the proliferative phase. In contrast, the addition of 200 or 400pg/ml of IL-6 induced significant inhibition of cell proliferation. Similarly, the addition of soluble IL-6 receptor caused significant suppression in the growth of endometrial stromal cells in tissue from the secretory phase, but not the proliferative phase. On the other hand, stromal cells of endometriotic tissues were resistant to IL-6, showing no inhibitory response. Although the combination treatment did not affect the proliferation of stromal cells of proliferative phase and of endometriotic tissues, 10gn/ml of soluble IL-6 inhibited proliferation of stromal cells of the secretory phase in the presence of 1ng/ml of soluble IL-6 receptor. The expression of transcripts of IL-6 receptor and gp130 was observed in the endometrial cells from the proliferative and secretory phases and in endometriotic cells. IL-6 may play a central role in regulation of the growth of endometrial cells as a mediator of endocrine action. Endometriotic cells may behave differently from the normal counterpart in terms of the inhibitory regulation exerted by IL-6. Less

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] T. Harada, H. Yoshioka, et al.: "Increased interleukin-6 levels in peritoneal fluid of infertile patients with active endometriosis"Am. J. Obstet Gynecol.. 176. 593-597 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Iwabe, T. Harada, et al.: "Pathogenetic significance of increased level of interleukin-8 in peritoneal fluid of patients with endometriosis"Fertil Steril. 69. 924-930 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Harada, H. Yoshioka, et al.: "Role of cytokines in progression of endometriosis"Gynecol. Obstet Invest.. 47 (suppl. 1). 34-40 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Yoshioka, T. Harada, et al.: "Menstrual cycle-specific inhibition in the proliferation of endometrial stromal cells by interleukin-6 and its soluble receptor"Am. J. Obstet Gynecol.. 180. 1088-1094 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Tsudo, T. Harada, et al.: "Altered gene expression and secretion of interleukin-6 instromal cells derived from endometriotic tissues"Fertil Steril. 73. 205-211 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Iwabe, T. Harada, et al.: "Tumor necrosis factor-α promotes proliferation of the endometriotic stromal cells by inducing interleukin-8 gene and protein expression"J. Clin. Endocrinol. Metab.. 85. 824-829 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Harada, H.Yoshioka, S.Yoshida, T.Iwabe, Y.Onohara, M.Tanikawa, N.Terakawa.: "Increased interleukin-6 levels in peritoneal fluid of infertile patients with active endometriosis"Am J Obstet Gynecol. 176. 593-7 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Iwabe, T.Harada, T.Tsudo, M.Tanikawa, Y.Onohara, N.Terakawa.: "Pathogenetic significance of increased levels of interleukin-8 peritoneal fluid of patients wit endometriosis"Fertil Steril. 69. 924-30 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Harada, A.Enatsu, M.Mitsunari, Y.Nagano, M.Ito, T.Tsudo, F.Taniguchi, T.Iwabe, M.Tanikawa, N.Terakawa.: "Role of cytokines in progression of endometriosis"Gynecol Obstet Incest. 47(suppl 1). 34-40 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H.Yoshioka, T.Harada, T.Iwabe, Y.Nagano, F.Taniguchi, M.Tanikawa, N.Terakawa.: "Menstral cycle-specific inhibition in the proliferation of endometrial stromal cells by interleukin-6 and its soluble receptor"Am J Obstete Gynecol. 180. 1088-94 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Tsudo, T.Harada, T.Iwabe, M.Tanikawa, Y.Nagano, F.Taniguchi, N.Terakawa.: "Altered gene expression and secretion of interleukin-6 in stromal cells derived from endometriotic tissues"Fertil Steril. 73. 205-211 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Iwabe, T.Harada, T.Tsudo, Y.Nagano, M.Tanikawa, N.Terakawa.: "Tumor necrosis factor-α promotes proliferation of the endometriotic stromal cells by inducing interleukin-8 gene and protein expression"J Clin Endocrinol Metab. 85. 824-829 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Harada.,H.Yoshioka et al.: "Increased interleukin-6 levels in peritoneal fluid of infertile patients with active endometriosis"Am J Chstet Gyneiol. 176(3). 593-597 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Iwabe,T.Harada et al.: "Pathogenetic significance of increased levels of interleukin-8 in peritoneal fluid of patients with endometriosis"Fertil Steril. 69(5). 924-930 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Harada,A.Enatsu et al.: "Role of cytokines in progression of endometriosis"Gynecol Obstet Invest. 47(suppl 1). 34-40 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Yoshioka,T.Harada et al.: "Menstral cycle-specific inhibition in the proliferation of endometrial stromal cells by interleukin-6 and its soluble receptor"Am J Obstet Gynecol. 180(5). 1088-1094 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Tsudo,T.Harada et al.: "Altered gene expression and secretion of interleukin-6 in stromal cells derived from endometriotic tissues"Fertil Steril. 73(2). 205-211 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] T,Iwabe,T.Harada,et al.: "Tumor necrosis factor-α promotes proliferation of the endometriotic stromal cells by inducing interleukin-8 gene and protein expression"J Clin Endocrinol Metab. 85(2). 824-829 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Tanikawa: "Expression of c-kit messenger ribonucleic acid in human oocyte and presence of soluble c-kit in follicular fluid." J Clin Endocrinol Metab. 83・4. 1239-1242 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] F.Taniguchi: "Paracrine effects of bFGF and KGF on the process of mouse blastocyst implantation." Mol Reprod Dev. 50・1. 54-62 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Iwabe: "Pathogenetic significance of increased levels of interleukin-8 in peritoneal fluid of patients with endometriosis." Fertil Steril. 69・5. 924-930 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Onohara: "Autocrine effects of transforming growth factor alpha on the development of preimplantation mouse embryo." J Assist Reprod Genet. 15・6. 395-402 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Yoshioka: "Menstral cycle-specific inhibition in the proliferation of endometrial stromal cells by interleukin-6 and its soluble receptor." Am J Obstete Gynecol. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Harada: "Role of cytokines in progression of endometriosis." Gynecol Obstet Invest. (in press).

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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