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Estrogen Receptor α Antagonists Mediate Changes in CCL 20 and CXCL 1 Secretions in the Murine Female Reproductive Tract
Author(s) -
Hickey Danica K.,
Fahey John V.,
Wira Charles R.
Publication year - 2013
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12021
Subject(s) - cxcl1 , ccl20 , endocrinology , estrogen receptor , estrogen , medicine , chemokine , biology , ovariectomized rat , receptor , chemistry , chemokine receptor , cancer , breast cancer
Problem Estradiol regulates chemokine secretion from uterine epithelial cells, but little is known about estradiol regulation in vivo or the role of estrogen receptors ( ER s). Method CCL 20 and CXCL 1 present in reproductive washes following treatment with selective estrogen receptor modulators ( SERM s) were compared with that during estrous and following estradiol‐treated ovariectomized BALB /c mice. Cellular regulation was determined using isolated vaginal and uterine epithelial/stromal cells in vitro . Results Uterine and vaginal chemokine secretion is cyclically regulated with CCL 20 at low levels but CXCL 1 at high levels during high estradiol, generally mimicking estradiol effect in vivo . ER α but not ER β regulated CCL 20/ CXCL 1 secretion by uterine epithelial cells in vitro and vaginal CCL 20 in vivo . Estradiol/ SERM s failed to alter uterine CCL 20 secretion in ovariectomized mice. Diminished uterine epithelial ER α staining following ovariectomy corresponded with estradiol unresponsiveness of uterine tissue. Conclusion Estrogen receptors α regulates CCL 20/ CXCL 1 secretion in the female reproductive tract, and ER α antagonists directly oppose the regulation by estradiol. Understanding ER ‐mediated antimicrobial chemokine expression is important to elucidate cyclic susceptibility to sexually transmitted pathogens.