Effects of combined 17beta-estradiol with TCDD on secretion of chemokine IL-8 and expression of its receptor CXCR1 in endometriotic focus-associated cells in co-culture

Abstract

Background: Chemokines play an important role in the pathogenesis of endometriosis. In the present study, the transcription of 18 chemokine receptors in eutopic endometrium and ectopic tissue with endometriosis was first analysed by RT-PCR. Dioxin, an air pollutant, and estrogen are reported to be associated with endometriosis. The regulatory mechanisms of dioxin and estrogen in the expression of CXCR1/IL-8 in the corresponding cells will help in elucidating roles of the chemokine in the aetiology of endometriosis.

Methods and results: CXCR1, a type of chemokine receptor, was over-expressed in endometriotic tissue. The high translation of the receptor and its ligand, interleukin (IL-8), in endometriotic tissue was then demonstrated by immunochemistry. Estradiol and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alone inhibited expression of CXCR1, whereas the combination of estradiol with TCDD up-regulated the expression. TCDD promoted IL-8 secretion by human pelvic mesothelial cells (HPMC), and 17beta-estradiol magnified the stimulatory effect. Both 17beta-estradiol and TCDD alone inhibited IL-8 secretion of U937 (a cell line of monocyte), but combination of 17beta-estradiol and TCDD had no further inhibitory effect. The co-culture of endometrial stromal cells (ESC) with HPMC produced more IL-8 than respective or total production of either of the cells alone, and estradiol played a synergistic stimulatory role with TCDD in IL-8 secretion of the co-culture. Interaction of HPMC and the monocytes significantly stimulated IL-8 secretion, suggesting a main resource of IL-8 in peritoneal cavity with endometriosis. TCDD promoted IL-8 secretion by HPMC-U937 co-culture, but exerted a contrary effect for IL-8 secretion when combined with estradiol.

Conclusion: Estradiol and TCDD in the peritoneal cavity can lead to a persistent and serious inflammation, which gives a new insight into the interactions of estrogen and TCDD in endometriosis.