Dioxin stimulates RANTES expression in an in-vitro model of endometriosis.

The industrial contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with inflammatory disorders in women and other mammals. The current studies were performed to investigate the effect of TCDD on RANTES expression in an in-vitro model of endometriosis. The biochemical effects of dioxins are mediated by binding to aryl hydrocarbon receptors (AhR). This study showed that both normal and endometriotic endometrial stromal cells express AhR protein, which was observed to be down-regulated by 40-60% after exposure to TCDD. Treatment with TCDD for 24 h increased the luciferase activity of the RANTES promoter by 2.5 +/- 1.0-fold in stromal cells derived from normal endometrium and endometriotic implants. When AhR were over-expressed in these cells, luciferase activity increased 6.1 +/- 1.4-fold, and RANTES protein secretion increased from undetectable to 31 +/- 10 pg/100,000 cells. TCDD failed to activate a RANTES construct with a mutated dioxin response element. Other AhR ligands had similar effects to TCDD on RANTES transcription and secretion. Control transfections using tumour necrosis factor (TNF)-alpha and nuclear factor (NF)-kappaB response element reporters indicated that these pathways are not activated by TCDD in endometrial stromal cells. This study has demonstrated that functional AhR are present in endometrial and endometriotic stromal cells and that TCDD up-regulates the expression of RANTES, providing a possible mechanistic link between dioxin exposure and chemokine expression in endometriosis.