Effect of antioxidants on cyclooxygenase-2 expression, prostaglandin synthesis and nuclear factor Kappa-B activity in human myometrium / 대한산부인과학회지

ABSTRACT

OBJECTIVE: 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.