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)
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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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