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.
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.


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.


CONCLUSIONS
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.
Shi
Ying-Li
YL
Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai 200011, China.
Luo
Xue-Zhen
XZ
Zhu
Xiao-Yong
XY
Hua
Ke-Qin
KQ
Zhu
Ying
Y
Li
Da-Jin
DJ
D000328:Adult; D002478:Cells, Cultured; D018920:Coculture Techniques; D004357:Drug Synergism; D004715:Endometriosis / Q000276:immunology* / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004785:Environmental Pollutants / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D023062:Receptors, Interleukin-8A / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020298:U937 Cells
D004785:Environmental Pollutants; D016209:Interleukin-8; D000072317:Polychlorinated Dibenzodioxins; D023062:Receptors, Interleukin-8A; D004958:Estradiol