Combination of 17β-estradiol with the environmental pollutant TCDD is involved in pathogenesis of endometriosis via up-regulating the chemokine I-309–CCR8

Objective To explore the effects of the combined E 2 with the environmental pollutant 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) on CCR8–I-309 expression by the endometriotic lesion-associated cells in the pathogenesis of endometriosis. Design Prospective laboratory study. Setting University hospital. Patient(s) Chinese women with endometriosis. Intervention(s) The endometriotic tissue and matched eutopic endometrium were collected. Endometrial stromal cells (ESCs), HPMC, and U937 cells were treated with 17β-E 2 or TCDD. The ESCs were stimulated with I-309. Main Outcome Measure(s) The expression of CCR8 in tissues was analyzed by reverse transcription–polymerase chain reaction and immunohistochemistry. The effect of I-309 on integrin β1 and αvβ3 expression intensity was analyzed by flow cytometry, and the chemotactic activity of I-309 on the ESC was explored by chemotactic assay. Concentration of I-309 in the culture supernatant was quantified by enzyme-linked immunosorbent assay. Result(s) CCR8 was overexpressed in the endometriotic tissue. I-309 promoted the expression of integrin β1. Estradiol and TCDD up-regulated CCR8 expression by ESCs. Estradiol magnified the stimulatory effect of TCDD on I-309 secretion by U937. The interaction of HPMC and U937 cells promoted I-309 secretion. Conclusion(s) These findings imply that the combination of 17β-E 2 with the environmental pollutant TCDD is involved in the pathogenesis of endometriosis via up-regulating the chemokine CCR8–I-309.