title: IL-1beta-mediated proinflammatory responses are inhibited by estradiol via down-regulation of IL-1 receptor type I in uterine epithelial cells.
abstract: The objective of this study was to examine the effects of sex hormones on IL-1beta-mediated responses by uterine epithelial cells. The mRNA expression and secretion of human beta-defensin-2 and CXCL8 by uterine epithelial cells was examined following stimulation with IL-1beta in the presence of estradiol or progesterone. Estradiol inhibited the IL-1beta-mediated mRNA expression and secretion of human beta-defensin-2 and CXCL8 by uterine epithelial cells while progesterone had no effect. Inhibition of the IL-1beta-mediated response by estradiol was dose dependent, with maximal inhibition observed using 10(-7) to 10(-10) M, and was shown to be mediated through the estrogen receptor because addition of a pure estrogen receptor antagonist abrogated this effect. The mechanism by which estradiol inhibits IL-1beta-mediated responses by uterine epithelial cells appears to be the down-modulation of the IL-1R type I, thereby reducing the uterine epithelial cell's ability to respond to IL-1beta. These results suggest that the inhibitory effect of estradiol on IL-1beta-mediated inflammatory responses by uterine epithelial cells indicates a link between the endocrine and immune systems and may be crucial for dampening proinflammatory responses during the time of ovulation or pregnancy.
authors.affiliation: Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756, USA. todd.m.schaefer@dartmouth.edu
authors.forename: Todd M
authors.initials: TM
authors.lastname: Schaefer
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Wright
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Pioli
authors.forename: Charles R
authors.initials: CR
authors.lastname: Wira
mesh_terms: D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D007375:Interleukin-1 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D053573:Receptors, Interleukin-1 Type I; D014599:Uterus / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D023083:beta-Defensins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D019743:Chemokines, CXC; C106641:DEFB4A protein, human; D007375:Interleukin-1; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D023083:beta-Defensins; D004958:Estradiol