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Korean Journal of Obstetrics & Gynecology 2002;45(10):1752-1757.
Published online October 1, 2002.
Role of Cyclooxygense-2 in Lipopolysacharide induced Matrix Metalloproteinase-2 and -9 expressions in human trophoblast (TL) cell line.
Jee Hyun Lee, Jong Chul Shin, Hyun Young Ahn, Dong Eun Yang, In Kwon, Gui SeRa Lee, Soo Pyung Kim
Department of Obstetrics and Gynecology, College of Medicine, Catholic University of Korea.
Abstract
OBJECTIVE
To evaluate whether lipopolysaccharide (LPS) modulates the expression of cyclooxy- genase-2 (COX-2) and also whether COX-2 is involved in the LPS induced matrix metalloproteinase-2 (MMP-2) and MMP-9 activation in human trophoblastic (TL) cell line. METHODS: We used the TL (trophoblast-like) cells and evaluated the effect of LPS on expression of COX-2 mRNA and protein and on activities of MMP-2 and MMP-9. Also, we pretreated cell line with LPS and NS398, a COX-2 inhibitor, and compared MMPs activities with LPS only group. In the present study, COX-2 was analyzed by RT-PCR and western blot analysis and gelatin zymography was done for the evaluation of gelatinase activities of MMP-2 and MMP-9. RESULTS: The mRNA and protein expressions of COX-2 were increased by LPS in time- and dose-dependant fashions. COX-2 mRNA expression began to rise from 1 hour of LPS treatment and was increased steadily thereafter. COX-2 protein expression was detected from 1 hour of LPS treatment, but maximally increased by the 3 hours of treatment. LPS also increased MMP-2 and MMP-9 activities in time and dose dependant fashions. Especially, active form of MMP-9 was observed in the high concentration of LPS (>50 microgram/ml). When adding COX-2 inhibitor (NS398) to LPS pretreated cell line, the MMPs activities increased in two or three fold compared to LPS only group. CONCLUSION: Our results suggested that LPS induces expression COX-2 and up-regulates activities of MMP-2 and MMP-9 in trophoblastic cell, but COX-2 although involved in LPS mediated MMP-2 and MMP-9 activation, may act through a different pathway than the commonly known prostaglandin metabolites mediated one.
Key Words: LPS, Trophoblast, MMP-2, MMP-9, COX-2


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