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Korean Journal of Obstetrics & Gynecology 2005;48(9):2103-2111.
Published online September 1, 2005.
Effect of antioxidants on cyclooxygenase-2 expression, prostaglandin synthesis and nuclear factor Kappa-B activity in human myometrium.
Yong Soo Seo, Soon Ha Yang, Cheong Rae Roh, Jong Hwa Kim
1Department of Obstetrics and Gynecology, Eulji University School of Medicine, Eulji General Hospital, Seoul, Korea.
2Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. jh369.kim@samsung.com
The oxidative stimuli activate NF-kappa B, which is a transcriptional factor inducing the expression of cyclooxygenase-2 (COX-2), an enzyme which involves in the rate-limiting step of prostaglandin (PG) synthesis. This study was performed to investigate whether vitamin C or caffeic acid phenethyl ester (CAPE) suppress COX-2 protein expression, PG synthesis, and NF-kappa B activity in human myometrium at term. METHODS: Human myometrial cells were cultured and stimulated with tumor necrosis factor-alpha (TNF-alpha), and also treated with TNF-alpha plus caffeic acid phenethyl ester, and TNF-alpha plus vitamin C. The expressions of COX-2 protein were assessed by western blot analyses. The activity of NF-kappa B was measured by luciferase assay. PGE2 production was determined by ELISA. RESULTS: The expression of COX-2 protein and the synthesis of PGE2 were promoted by TNF-alpha and peaked after 6 hours of exposure. CAPE and vitamin C significantly inhibited the TNF-alpha-dependent expression of COX-2 protein and the synthesis of PGE2. NF-kappa B activities were also suppressed by the addition of CAPE and vitamin C to TNF-alpha pre-stimulated cells. CONCLUSION: The antioxidants, CAPE and vitamin C, inhibited COX-2 expression, PGE2 synthesis and NF-kappa B activity in human myometrial cells. These results suggest that the antioxidant may play an inhibitory role in human labor.
Key Words: Antioxidant, Myometrium, Cytokine, NF-kappa B, Cyclooxygenase-2, Prostaglandin
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