title: 17{beta}-Estradiol modulates the macrophage migration inhibitory factor secretory pathway by regulating ABCA1 expression in human first-trimester placenta.
abstract: Successful pregnancy involves a series of events, most of them mediated by hormones and cytokines. Estrogens, besides being important for placental growth and embryo development, have a marked effect on the immune system exerting either pro- or anti-inflammatory properties. Numerous studies suggest that estrogens directly affect cellular function, including cytokine production. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in pregnancy, particularly during the earlier stages of placentation. Since reports on mice have shown that estrogens modulate MIF, herein we investigated the effect of estrogens on human placental MIF. By using an in vitro model of first-trimester chorionic villous explants, we found that 17beta-estradiol (E(2)) was able to modulate the release of MIF in a dose-dependent manner (10(-12) vs. 10(-9) M, P < 0.05; 10(-9) vs. 10(-5) M, P < 0.05; 10(-12) vs. 10(-5) M, P < 0.001). Unlike MIF release, no significant change in tissue MIF protein or MIF mRNA was observed. We showed evidence that E(2) concentrations (10(-9) and 10(-5) M) act on placental tissue downregulating the mRNA and protein expression of the ATP-binding cassette transporter protein A1, a membrane transporter involved in MIF secretion. These findings emphasize the mutual cooperation between hormones and cytokines and suggest that increasing estrogen levels with advancing gestation may have a major role in regulating placental MIF secretion.
authors.affiliation: Dept. of Physiology, Univ. of Siena, Italy. ietta@unisi.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Ietta
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bechi
authors.forename: Roberta
authors.initials: R
authors.lastname: Romagnoli
authors.forename: Jayonta
authors.initials: J
authors.lastname: Bhattacharjee
authors.forename: Massimo
authors.initials: M
authors.lastname: Realacci
authors.forename: Maura
authors.initials: M
authors.lastname: Di Vito
authors.forename: Cristina
authors.initials: C
authors.lastname: Ferretti
authors.forename: Luana
authors.initials: L
authors.lastname: Paulesu
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism*; D011261:Pregnancy Trimester, First / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008263:Macrophage Migration-Inhibitory Factors; D004958:Estradiol