Context: The nuclear factor-kappaB (NF-B) pathway is a critical mediator of RANTES (Regulated on Activation, Normal T cell Expressed and Secreted) 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 anti-inflammatory drug sulindac on NF-B activation, NF-B mediated gene expression, RANTES gene and protein expression in endometrial stromal cells isolated from women with endometriosis and unaffected controls.

Design: Clinical experimental study

Setting: University Hospital

Results: The inflammatory response in endometriosis is augmented as shown by a 5-fold increased TNF- 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-B in endometriotic cells, which could be suppressed by sulindac. Electromobility shift assays showed that sulindac dramatically decreased NF-B activation and diminished TNF- and interleukin (IL)-1 induced NF-B DNA binding activity. Sulindac pretreatment resulted in a significant decrease in TNF--induced luciferase activity of NF-B response element and -477 bp RANTES promoter constructs in normal and endometriotic stromal cells. The addition of sulindac to IL-1 and TNF- treated endometriotic stromal cells also resulted in a 4-fold inhibition of RANTES protein secretion (P < 0.05).

Conclusions: We have demonstrated that the sulindac exerts strong anti-inflammatory effects by suppression of NF-B translocation, inhibition of NF-B mediated gene transcription, RANTES gene expression and protein secretion in normal and endometriotic stromal cells. These results suggest that drugs targeting the NF-B pathway may be beneficial in the treatment of endometriosis-associated symptoms.