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The basic study on new treatment for cervical maturation and preterm labor using cytokine

Research Project

Project/Area Number 10671529
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionHamamatsu University School Of Medicine

Principal Investigator

KANAYAMA Naohiro  Hamamatsu Univ. School of Medicine, Dept. Obstet & Gynecol, Professor, 医学部, 教授 (70204550)

Co-Investigator(Kenkyū-buntansha) TOKUNAGA Naoki  Hamamatsu Univ. School of Medicine, Dept. Obstet & Gynecol, Assistant, 医学部・附属病院, 助手 (20283369)
SUMIMOTO Kazuhiro  Hamamatsu Univ. School of Medicine, Dept. Obstet & Gynecol, Assistant, 医学部, 助手 (30126817)
寺尾 俊彦  浜松医科大学, 副学長 (60022852)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsCervical maturation / Interleukin-8 / DHEA-S / Hyalaronic acid / Urinary trypsin inhibitor / IL-8 receptor / P57kip2 / 頚管炎 / 早産 / p57kip2 / 子宮収縮 / ヘパリン / ヒアルロン酸 / インターロイキン-8レセプター / インターαトリプシンインヒビター
Research Abstract

The aim of this research was to develop a new treatment for regulation of cervical maturation. In rabbit experiments suppositories with interleukin-8 (IL-8) produced a marked cervical maturation in various cytokine supppositories. Inteleukin-1 (IL-1) suppositories induced a prominent uterine contractions. Suppositories with IL-8+IL-1 produced contractile response with increased frequency. Our data suggest that IL-8 does not only induce cervical maturation, but it also stimulates IL-1 induced uterine contraction. IL-8 plays a key role in an important process during labor and delivery.
We also studied the modification factors to express IL-8. Dehydroepiandrosterone sulfate (DHEA-S) is produced from fetal adrenal grand during pregnancy. We found that DHEA-S stimulated the IL-8 expression. Its mechanism was mainly due to promotion of IL-8 receptor. Heparan sulfate accelerated cervical maturation through upregulation of autocrine system of IL-8. Hyaluronic acid especially low molecular hyaluronic acid activated IL-8 expression. From the aspects of clinical base seminal plasma stimulated the production of IL-8 from the cervical tissue. It suggests that sexual intercourse is a risk factor for preterm labor.
Urinary trypsin inhibitor (UTI) inhibited cervical maturation. Its mechanism is mainly ascribed to inhibition of IL-8 expression of cervical cells. UTI also inhibited uterine muscle contraction due to suppression of calcium influx. UTI concentration is extremely high in amniotic fluid. Fetus expelled UTI to amniotic fluid profoundly. Thus, UTI is a specific substance of fetus. UTI may open anew aspect for the treatment of preterm labor.
P57kip2 regulates G1 cyclin. We found that P57kip2 knock out mice occurred pretem delivery. P57kip2 showed a marked proliferation of trophoblasts. This P57kip2 knock out mice may give a new way for the research of preterm delivery

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Naohiro Kanayama: "P57^<kip2> regulates the proper development of labyrinthine and spongio trophoblasts"Molecular Human Reproduction. 6. 1019-1025 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Naohiro Karayama: "Pharmacologic doses of interleukin-8 suppositories induce follicular maturation in rabbits"Cytokines. 12. 361-367 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Belayet BMd, Kanayama N, Khatun S, el Maradny E, Masui M, Tokunaga N, Sumimoto K, Kobayashi T, Terao T: "Decreased renal and hepatic blood flow with pre-eclampsia-like histological changes was obtained by stimulation of the celiac ganglion with LPS."Am J Perinat. 15. 109-114 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kanayama N, Maehara K, She L, Belayet BMd, Khatun S, Tokunaga N, Terao T.: "Urinary trypsin inhibitor suppresses vascular smooth muscle contraction by inhibition of Ca2+ influx."Biochimica Biophysica Acta. 1381. 139-146 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kanayama N, el Maradny E, Goto J, Terao T.: "Effect of dehydroepiandrosterone sulfate on interleukin-8 receptor during cervical ripening."Euro J Endocrin. 138. 587-593 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kanayama N, Khatun S, Terao T.: "The effect of urinary trypsin inhibitor on uterine muscle contraction and cervical maturation."Trophoblastic Res. 18. 415-425 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Khatun S, Kanayama N, Belayet BMd, Yonezawa M, Kobayashi T, Terao T.: "Interleukin-8 (IL-8) potentiate the effect of IL-1-Induced Uterine Contraction."Hum Reprod. 14. 560-565 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Belayet BMd, Kanayama N, Khatun S, Sumimoto K, Kobayashi T, Terao T.: "Binding to heparan sulfate intensifies neutrophil responses to interleukin-8 thus enhances cervical maturation in rabbits"Mol Hum Reprod. 5. 261-269 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Belayet BMd, Kanayama N, Khatun S, Sumimoto K, Kobayashi T, Terao T.: "Dehydroepiandrosteron sulfate promotes hyaluronic acid-induced cervical ripening in rabbits."Hum Reprod. 14. 1361-1367 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kanayama N, Goto J, Terao T.: "The role of low-molecular-weight hyaluronic acid contained in Wharton's jelly in necrotizing funisitis."Pediat Res. 45(4pt1). 510-514 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Belayet BMd, Kanayama N, Khatun S, Asahina T, Okada Y, Kutamura K, Kobayashi T, Terao T.: "Pharmacologic doses of interleukin-8 suppositories induce follicular maturation in rabbits"Cytokines. 12. 361-367 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takahashi K, Kobayashi T, Kanayama N.: "p57kip2 regulates the proper development of labyrinthine and spogiotrophoblasts."Mol Hum Reprod. 6. 1019-1025 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Naohiro Kanayama: "P57^<Kip2> regulates the proper development of labyrinthine and spongiotrophoblastss"Molecular Human Reproduction. 6. 1019-1025 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Naohiro Kanayama: "Pharmacologic doses of interleukin & suppositories induce follicular maturation in rabbits"Cytokines. 12. 361-367 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Naohiro Kanayama: "The role of low molecular weight hyaluronic acid contained in Wharton's jelly in necrotizing fun*sitis"Pedia.. 45. 510-514 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Selina Khatan: "Interlewkin-8 potenitiates the effect of interlewkin-1-induced uterine contraction"Human Reproduction. 14. 560-565 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hossain Md Belayet: "Dehydroepiandrosterone ***phate promotes hyaluronic acid-induced cer*ical ripenim* in rabbits"Human Reproduction. 14. 1361-1367 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hossain Md Belayet: "Binding of interlewkin-8 to heparan sulphate enhances cer***l matatralion in rabbits"Molecular Human Reproduction. 5. 261-269 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Naohiro Kanayama et al.: "Effect of dehydroepiandrosterone sulfate on interleukin-8 receptor daring cervicd ripening" European Journal of Endcrinology. 138. 587-593 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Naohiro Kanayama et al.: "Urinary trypsin inhibitor suprresses vascular smouth muscle comtraction by inhibition of Ca^<2+> in flux" Biochimica of Biophysica Acta. 1381. 139-146 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 金山 尚裕: "分娩発来とサイトカイン" 周産期学シンポジウム. 16. 85-94 (1998)

    • Related Report
      1998 Annual Research Report

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

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