Sulindac suppresses nuclear factor-kappaB activation and RANTES gene and protein expression in endometrial stromal cells from women with endometriosis
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Updated: Aug 16, 2026
Isolation of Human Endometrial Stromal Cells for In Vitro Decidualization
Published on: September 1, 2018
Fritz Wieser1, Jean-Louis Vigne, Isabelle Ryan
1Division of Gynecological Endocrinology and Reproductive Medicine, University of Vienna, Austria.
Context:
The nuclear factor-kappaB (NF-kappaB) pathway is a critical mediator of RANTES (regulated on activation, normal T cell expressed and secreted) gene regulation and therefore represents a potential target for therapy of endometriosis-associated symptoms.
Objective:
The objective of this study was to investigate the effects of the antiinflammatory drug sulindac on NF-kappaB activation, NF-kappaB-mediated gene expression, RANTES gene and protein expression in endometrial stromal cells isolated from women with endometriosis, and unaffected controls.
Design:
This was a clinical experimental study.
Setting:
The study was conducted at a university hospital.
Results:
The inflammatory response in endometriosis is augmented by a 5-fold increased TNFalpha-induced RANTES secretion from ectopic endometriotic stromal cells, compared with normal endometrial stromal cells (P < 0.05). Western blot analysis revealed basal activation of NF-kappaB in endometriotic cells, which could be suppressed by sulindac. EMSAs showed that sulindac dramatically decreased NF-kappaB activation and diminished TNFalpha and IL-1beta-induced NF-kappaB DNA binding activity. Sulindac pretreatment resulted in a significant decrease in TNFalpha-induced luciferase activity of NF-kappaB response element and -477 bp RANTES promoter constructs in normal and endometriotic stromal cells. The addition of sulindac to IL-1beta- and TNFalpha-treated endometriotic stromal cells also resulted in a 4-fold inhibition of RANTES protein secretion (P < 0.05).
Conclusions:
We have demonstrated that sulindac exerts strong antiinflammatory effects by suppression of NF-kappaB translocation, inhibition of NF-kappaB-mediated gene transcription, RANTES gene expression, and protein secretion in normal and endometriotic stromal cells. These results suggest that drugs targeting the NF-kappaB pathway may be beneficial in the treatment of endometriosis-associated symptoms.
Insights
The anti-inflammatory drug sulindac effectively reduces NF-kappaB activation and RANTES gene and protein expression in endometriosis. This suggests sulindac may be a beneficial treatment for endometriosis symptoms by targeting the NF-kappaB pathway.
Area of Science:
- Endocrinology and Reproductive Medicine
- Inflammation and Immunology
Background:
- The nuclear factor-kappaB (NF-kappaB) pathway is integral to regulating RANTES (regulated on activation, normal T cell expressed and secreted) gene expression.
- This pathway's role in RANTES regulation presents a potential therapeutic target for endometriosis-associated symptoms.
Purpose of the Study:
- To evaluate the impact of the anti-inflammatory drug sulindac.
- To investigate sulindac's effects on NF-kappaB activation and NF-kappaB-mediated gene expression.
- To examine sulindac's influence on RANTES gene and protein expression in endometrial stromal cells from women with and without endometriosis.
Main Methods:
- A clinical experimental study design was employed.
- The study was conducted at a university hospital setting.
- Methods included Western blot analysis, Electrophoretic Mobility Shift Assays (EMSAs), and luciferase reporter assays.
Main Results:
- Endometriotic stromal cells exhibited a 5-fold increase in TNFalpha-induced RANTES secretion compared to normal cells.
- Sulindac suppressed basal NF-kappaB activation in endometriotic cells and diminished TNFalpha and IL-1beta-induced NF-kappaB DNA binding activity.
- Sulindac significantly decreased TNFalpha-induced RANTES promoter activity and inhibited RANTES protein secretion by 4-fold in endometriotic stromal cells.
Conclusions:
- Sulindac demonstrates potent anti-inflammatory effects through suppression of NF-kappaB translocation and RANTES expression.
- Inhibition of NF-kappaB-mediated gene transcription, RANTES gene expression, and protein secretion was observed in both normal and endometriotic stromal cells.
- Targeting the NF-kappaB pathway with drugs like sulindac may offer therapeutic benefits for endometriosis symptoms.
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