Constitutive and tumor necrosis factor-α-induced activation of nuclear factor-κB in adenomyosis and its inhibition by andrographolide

Objective: To investigate the action of nuclear factor (NF)-kappa B in adenomyosis and evaluate the potential therapeutic effect of andrographolide on tumor necrosis factor (TNF)-alpha-induced expression of NF-kappa B-mediated genes cyclooxygease-2 (COX-2), vascular endothelial growth factor (VEGF), and tissue factor (TF) in adenomyotic stromal cells. Design: Laboratory study using human tissues. Setting: Academic hospital. Patient(s): Twenty-nine patients (cases) with histologically confirmed adenomyosis and 14 (controls) without adenomyosis or endometriosis. Intervention(s): Endometrial stromal cells derived from tissue samples harvested from both cases and controls were subjected to electrophoretic mobility shift assay, and gene and protein expression analyses. Main Outcome Measure(s): The NF-kappa B DNA-binding activity and protein levels of NF-kappa B subunits p50 and p65 and the messenger RNA (mRNA) and protein levels of NF-kappa B-mediated genes COX-2, VEGF, and TF in cases and controls, and their changes after stimulation with TNF-alpha and treatment with andrographolide. Result(s): The constitutive NF-kappa B DNA-binding activity and protein expression levels of p50 and p65, and mRNA and protein levels of COX-2, VEGF, and TF in cases were significantly higher than that of controls. The binding activity level correlated positively with dysmenorrhea severity in cases. The TNF-alpha stimulation further increased the binding activity, and the mRNA and protein levels of COX-2, VEGF, and TF, but treatment with andrographolide significantly reduced them. Conclusion(s): NF-kappa B may be a pivotal transcription factor involved in the development of adenomyosis. Targeting NF-kappa B with inhibitors, like andrographolide, may hold promises of treating adenomyosis. (C) 2013 by American Society for Reproductive Medicine.