Combination of 17beta-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.


METHODS
Prospective laboratory study.


METHODS
University hospital.


METHODS
Chinese women with endometriosis.


METHODS
The endometriotic tissue and matched eutopic endometrium were collected. Endometrial stromal cells (ESCs), HPMC, and U937 cells were treated with 17beta-E(2) or TCDD. The ESCs were stimulated with I-309.


METHODS
The expression of CCR8 in tissues was analyzed by reverse transcription-polymerase chain reaction and immunohistochemistry. The effect of I-309 on integrin beta1 and alphavbeta3 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.


RESULTS
CCR8 was overexpressed in the endometriotic tissue. I-309 promoted the expression of integrin beta1. 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.


CONCLUSIONS
These findings imply that the combination of 17beta-E(2) with the environmental pollutant TCDD is involved in the pathogenesis of endometriosis via up-regulating the chemokine CCR8-I-309.
Shi
Ying-Li
YL
Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
Luo
Xue-Zhen
XZ
Zhu
Xiao-Yong
XY
Li
Da-Jin
DJ
D002478:Cells, Cultured; D054402:Chemokine CCL1; D019742:Chemokines, CC / Q000235:genetics* / Q000378:metabolism; D004338:Drug Combinations; D004715:Endometriosis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism; D020298:U937 Cells; D015854:Up-Regulation; D014591:Uterine Diseases / Q000139:chemically induced* / Q000235:genetics
C065971:CCL1 protein, human; C103330:CCR8 protein, human; D054402:Chemokine CCL1; D019742:Chemokines, CC; D004338:Drug Combinations; D004785:Environmental Pollutants; D019012:Integrin beta1; D000072317:Polychlorinated Dibenzodioxins; D054401:Receptors, CCR8; D019707:Receptors, Chemokine; D004958:Estradiol