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Korean Journal of Obstetrics & Gynecology 2005;48(3):638-650.
Published online March 1, 2005.
Pro-inflammatory cytokine-induced nuclear factor-kappa B activity in prelabor and in-labor myometrial cells at term gestation.
Soon Ha Yang, Hee Chul Syn
Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, Korea. hbk8392@yahoo.co.kr
The objectives of this study were to determine whether NF-kappa B-mediated pro-inflammatory cytokines signaling leads to COX-2 expression and PGE2 synthesis in human myometrial cells at term, and to compare cytokines-induced NF-kappa B activity and subsequent COX-2 expression and PGE2 synthesis between prelabor and in-labor myometrial cells. METHODS: Ten samples of human myometrium were obtained from 5 pregnant women with no labor and 5 in labor at term during cesarean section. Myometrial smooth muscle cells were harvested by cell culture and stimulated with TNF-alpha. PGE2 production and COX-2 expression were determined by ELISA and Western blotting analysis, respectively. NF-kappa B transcriptional activity was assessed by luciferase assay and by nuclear shifting using EMSA. RESULTS: Before the treatment of TNF-alpha, the levels of PGE2 production, COX-2 expression, and activity and nuclear shift of NF-kB in in-labor cells were higher than those in prelabor cells. By the stimulation of TNF-alpha, PGE2 output, COX-2 expression, and activity and nuclear shift of NF-kappa B increased in both of prelabor and in-labor cells. The increases of PGE2 production, COX-2 expression, and NF-kappa B activity were significantly greater in in-labor cells. CONCLUSION: Pro-inflammatory cytokines-induced COX-2 expression and subsequent PG synthesis, mediated by NF-kappa B, appears one of the important mechanisms of labor in term gestation.
Key Words: Nuclear factor kappa B, Pro-inflammatory cytokines, Cyclooxygenase-2, Prostaglandin, Term gestation, Labor
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