| Co-Investigator(Kenkyū-buntansha) |
HIROTA Naoyoshi Nippon Organon K.K., Res & Develop Division, Head, 医薬研究所, 研究開発管理室長
KARIYA Masatoshi Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (90243013)
ITOH Hiroaki Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 助手 (70263085)
WADA Yukihisa Nippon Organon K.K., Res & Develop Division, Staff, 医薬研究所, 研究員
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| Research Abstract |
The matrix metalloproteinases (MMPs) mediated degradation of collagen fibril is thought to be one of key events in the complicated process of cervical ripening. In this study, we investigated the expression of MMP-1, 2, 9 as well as inducible and endothelial nitric oxide synthase (iNOS and eNOS) in the human uterine cervix and the possible effect of PGF2α, IL-1αand nitric oxide on MMPs production from cultured human uterine cervical fibroblast (CxF) cells. The present study suggested that PGF2α, IL-1α, and nitric oxide contribute to the process of cervical ripening via enhancement of MMP-1 production.
During active labor, cervical tissue is distended by presenting part of the fetus. In this study, we investigated the effects of cyclic mechanical stretch on the production of MMP-1, 2, 9 from cultured human uterine cervical fibroblast cells. Cyclic mechanical stretch specifically enhanced the mRNA expressions and secretion of MMP-1. The present study suggested that mechanical stretch cont
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ribute to the process of cervical ripening via enhancement of MMP-1 production.
Leukocyte infiltration into the cervix is also a characteristic feature of parturition. In the present study, we examined the effect of cyclic mechanical stretch on secretion of chemokines (IL-8 and MCP-3) from cultured human uterine cervical fibroblast (CxF) cells. IL-8 and MCP-3 proteins and mRNAs were all detected n the human uterine cervices. These substances were positively stained in cervical stromal cells. The IL-8 and MCP-3 mRNA expression in the CxF cells significantly increased to approximately 8 and 3-folds after stimulation with cyclic mechanical stretch for 12 hours, respectively, (both P<0.005). IL-8 and MCP-3 levels in the culture medium of CxF cells after cyclic mechanical stretch for 24 hours were significantl,higher. than those without the stimulation (both P<0.005). Such enhancement of IL-8 and MCP-3 secretion by cyclic mechanical stretch was significantly inhibited by co-treatment with curcumin, an AP-1 inhibitor.
Cyclic mechanical stretch by fetal presenting part during labor may initiate or facilitate cervical ripening through augmentation of production of IL-8 and MCP-3 followed by infiltration of neutrophils and monocyte/macrophage in the uterine cervix. Less
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