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

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.

• Authors: Bin Li, Ming Chen, Xishi Liu, Sun-Wei Guo
• Journal: Fertility and sterility (Fertil Steril) Vol. 100 Issue 2 Pg. 568-77 (Aug 2013) ISSN: 1556-5653 [Electronic] United States
• PMID: 23706331 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Diterpenes
• NF-kappa B
• Tumor Necrosis Factor-alpha
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• andrographolide
• Thromboplastin
• Cyclooxygenase 2
• PTGS2 protein, human

Topics

• Adenomyosis (genetics, pathology)
• Adult
• Anti-Inflammatory Agents (pharmacology)
• Case-Control Studies
• Cyclooxygenase 2 (genetics, metabolism)
• Diterpenes (pharmacology)
• Down-Regulation (drug effects)
• Humans
• Middle Aged
• NF-kappa B (genetics, metabolism)
• Thromboplastin (genetics, metabolism)
• Transcriptional Activation (drug effects)
• Tumor Necrosis Factor-alpha (pharmacology)
• Vascular Endothelial Growth Factor A (genetics, metabolism)