Dioxin stimulates RANTES expression in an in-vitro model of endometriosis
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This study demonstrates that dioxin (TCDD) up-regulates RANTES expression in both normal and endometriotic endometrial stromal cells via the aryl hydrocarbon receptor (AhR).
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Abstract
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.
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Cited by (17)
- Evidence of Dioxin as Endocrine Disrupting Chemicals in the Development of Endometriosis: A Narrative Review 2023
- Progesterone Resistance in Endometriosis: Current Evidence and Putative Mechanisms 2023
- Associations between Exposure to Organochlorine Chemicals and Endometriosis: A Systematic Review of Experimental Studies and Integration of Epidemiological Evidence 2021
- Progesterone resistance in endometriosis: origins, consequences and interventions 2017
- Functional expression of aryl hydrocarbon receptor on mast cells populating human endometriotic tissues 2016
- Estrogen receptor β agonist inhibits proliferation of endometrial stromal cells in an estrogen-receptor independent manner 2014
- Environmental Influences on the Development of Endometriosis 2013
- Chemokines in the pathogenesis of endometriosis and infertility 2013
- The role of NF-kappaB in endometriosis 2012
- Endometriosis and Autoimmunity 2011
- O papel dos desreguladores endócrinos na fisiopatologia da endometriose: revisão da literatura 2010
- Combination of estrogen and dioxin is involved in the pathogenesis of endometriosis by promoting chemokine secretion and invasion of endometrial stromal cells 2008
- Dioxin may promote inflammation-related development of endometriosis 2008
- The link between environmental toxicant exposure and endometriosis 2007
- Combination of 17β-estradiol with the environmental pollutant TCDD is involved in pathogenesis of endometriosis via up-regulating the chemokine I-309–CCR8 2007
- Effects of combined 17β-estradiol with TCDD on secretion of chemokine IL-8 and expression of its receptor CXCR1 in endometriotic focus-associated cells in co-culture 2006
- Sulindac Suppresses Nuclear Factor-κB Activation and RANTES Gene and Protein Expression in Endometrial Stromal Cells from Women with Endometriosis 2005
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