Project/Area Number |
02454382
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Research Category |
Grant-in-Aid for General Scientific Research (B)
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Allocation Type | Single-year Grants |
Research Field |
Obstetrics and gynecology
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Research Institution | Osaka University |
Principal Investigator |
MATSUZAKI Noboru Osaka University Med. School, Dept of obste & GYN, Aesist prof., 医学部, 助手 (30199781)
|
Co-Investigator(Kenkyū-buntansha) |
OHASHI Kazutomo Osaka Univ Med. School. Dep of OB & GYN, Assist. prof, 医学部, 助手 (30203897)
KOYAMA Masayasu Osaka Univ. Med. School. Dept of OB & GYN, Assist. prof, 医学部, 助手 (00183351)
SAJI Fumitaka Osaka Univ. Med. School, Dept. of Ob & GYN. Lecturer., 医学部, 講師 (90093418)
|
Project Period (FY) |
1990 – 1991
|
Project Status |
Completed (Fiscal Year 1991)
|
Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1991: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1990: ¥4,200,000 (Direct Cost: ¥4,200,000)
|
Keywords | Interleukin-6 (IL-6) / IL-6-receptor / Interleukin-1 / TNF-alpha / TGF-beta (transforming grothfactor) / hCG (human chorionic gonadotropin (hCG) / trophoblasts / placental Hormone / インタ-ロイキン(ILー6) / ILー1(interleukinー1) / TNFーα(tumor necusis factorーα) / TGFーβ(transtorming growth factorーβ) / hCG(human chonoue gonadotropn) / 絨毛細胞 / インタ-ロイキン6レセプタ- / 絨毛性ゴナドトロピン / インタ-ロイキン1 / 腫瘍壊死因子(TNFーα) |
Research Abstract |
Trophoblast in the placenta produce human chorionic gonadotropin (hCG) , one of representative Placental hormones, during pregnancy. hCG production has been demonstrated to be regulated by reagents such as gonadotropin-releasing hormone (GnRH) and epidermal growth factor (EGF) , We have reported that Trophoblasts produce interleukin-6 (IL-6) and express IL-6 receptor on the surface membrane. Stimulation of IL-6-R with IL-6 resulted in hCG release by 1st trimester human trophoblasts, demonstrating IL-6 and IL-6-R-mediated regulation of hCG release. To examine the effect of two other cytokines, IL-1 and tumor necrosis factor-alpha (TNF-alpha), on placental hCG release, trophoblast were stimulated with IL-1 and TNF-alpha, Both cytokines were capable of synergistically stimulating hCG release though IL-6 release and IL-6-Reactivation, Transforming growth factor-beta (TGF-beta) , in contrast, suppressed hCG release by inhibitine IL-6 release and IL-6-R-mediated function. Four choriocarcinoma cell lines were examined for their capacity to release hCG in response to the cytokines like IL-1, TNF-alpha and IL-6. Two choriocarcinoma cell likes (Jar and HCCM-5) showed IL-1-induced but not TNF-alpha-induced hCG release, retaining the partial capacity of cytokine networks in proction of hCG. The signal Transduction pathway for cytokine-mediated hCG was examined by second messenger homologues and protein kinase inhibitors. IL-6-induced hCG release was blocked by genistein, a tywine kinase inhibitor, but not by any other kinds of inhibitors. IL-1- and TNF-alpha-induced hCG releases were also blocked by geistern. However, the cytokine-induced IL-6 releases were not blocked by genistlin. Farther experiments are underway in our laboratory to characterize IL-1-and TNF-alpha-induced IL-6 re lease.
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