2007 Fiscal Year Final Research Report Summary
DEVELOPMENT OF A NOVEL THERAPEUTIC DRUG FOR TREATMENT OF PRETERM DELIVERY
| Project/Area Number |
18591791
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Hirosaki University |
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Principal Investigator |
TANAKA Kanji Hirosaki University, Hirosaki University School of Medicine Department of Obstetrics and Gynecology, Assistant Professor (20311540)
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| Co-Investigator(Kenkyū-buntansha) |
HIGUCHI Tsuyoshi Hirosaki University School of Medicine Department of Obstetrics and Gynecology, 医学部附属病院, Assistant Professor (60238285)
OZAKI Takashi Hirosaki University School of Medicine Department of Obstetrics and Gynecology, 医学部附属病院, Associate Professor (80260404)
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| Project Period (FY) |
2006 – 2007
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| Keywords | preterm delivery / proteoglycan / inflammatory cytokine / cultured fibroblast from human uterine cervix / chorioamnionitis / urinastatin |
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| Research Abstract |
Objectives: Chorioamnionitis (CAM) is an extremely important factor in preterm delivery, and various inflammatory cytokines of amnionic fluid have important roles in the onset of CAM and cervical ripening. Proteoglycan (PG) was a main component of the extracellular matrix and its anti-inflammatory effects have attracted particular attention. In this study, the effect of PG on inflammatory cytokines was investigated in LPS-stimulated cultured fibroblasts from the uterine cervix.
Marerials and Methods: A specimen of normal human uterine cervix was collected after a total hysterectomy for uterine myoma at Hirosaki University Hospital. This tissue sample was cut into small pieces, which were then incubated in Dulbecco's modified Eagle medium containing 10% fetal bovine serum in a humidified atmosphere 5% CO_2/95% air at 37℃. After the fibroblasts had grown to confluency, they were used at up to sixth passage for the following experiments. Uterine cervical fibroblasts were incubated with or
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without Proteoglycan (0.5 mg/ml, 1 mg/ml) and LPS (1 μ g/ml) for 48 h, and a medium fraction was obtained. The amounts of IL-1β, IL-6 and IL-8 in the medium were assayed by the ELISA method.
Results: In the medium, the amount of IL-1β produced by cultured fibroblasts from the uterine cervix increased and reached a peak 12 hours after the addition of LPS, but later this amount decreased gradually. The addition of PG to the medium of cultured cells reduced IL-1β in a dose-dependent manner. Incubated with 1 mg/ml PG and LPS, IL-1β was suppressed by 58% compared with the controls. The amount of IL-6 produced by the same cell in the amount of IL-6 in a dose-dependent manner. Incubated with 1 mg/ml PG and LPS, IL-6 was significantly decreased in comparison with the controls at all times. The amount of IL-8 produced by the same cell in the medium increased linearly with time, but IL-8 production decreased with an increase in PG concentration. In the presence of 0.5 and 1.0 mg/ml PG, IL-8 production was decreased by about 20% and 30.1% of the control level.
Conclusions: The results of the current study indicate that preterm delivery may be suppressed by PG since it inhibited various inflammatory cytokines that mainly contribute to the onset of CAM and cervical ripening. Less
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