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

Capsule:
The transcription factor NF-kB is found to be constitutively activated in adenomyosis and its activation level correlates positively with the severity of dysmenorrhea in women with adenomyosis.

Authors:
Bin Li, M.S., Ming Chen, Ph.D., Xishi Liu, M.D., Ph.D., Sun-Wei Guo, Ph.D.

Volume 100, Issue 2, Pages 568-577, August 2013

Abstract:

Objective:
To investigate the action of nuclear factor (NF)-κB in adenomyosis and evaluate the potential therapeutic effect of andrographolide on tumor necrosis factor (TNF)-α-induced expression of NF-κB-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-κB DNA-binding activity and protein levels of NF-κB subunits p50 and p65 and the messenger RNA (mRNA) and protein levels of NF-κB-mediated genes COX-2, VEGF, and TF in cases and controls, and their changes after stimulation with TNF-α and treatment with andrographolide.

Result(s):
The constitutive NF-κB 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-α 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-κB may be a pivotal transcription factor involved in the development of adenomyosis. Targeting NF-κB with inhibitors, like andrographolide, may hold promises of treating adenomyosis.

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