Role of Cyclooxygense-2 in Lipopolysacharide induced Matrix Metalloproteinase-2 and -9 expressions in human trophoblast (TL) cell line.
- Author:
Jee Hyun LEE
1
;
Jong Chul SHIN
;
Hyun Young AHN
;
Dong Eun YANG
;
In KWON
;
Gui SeRa LEE
;
Soo Pyung KIM
Author Information
1. Department of Obstetrics and Gynecology, College of Medicine, Catholic University of Korea.
- Publication Type:Original Article
- Keywords:
LPS;
Trophoblast;
MMP-2;
MMP-9;
COX-2
- MeSH:
Blotting, Western;
Cell Line*;
Gelatin;
Gelatinases;
Humans*;
Matrix Metalloproteinase 2*;
Matrix Metalloproteinases;
RNA, Messenger;
Trophoblasts*
- From:Korean Journal of Obstetrics and Gynecology
2002;45(10):1752-1757
- CountryRepublic of Korea
- Language:Korean
-
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.