196,024 research outputs found

    ESTROGENS MODULATE MACROPHAGE MIGRATION INHIBITORY FACTOR(MIF) EXPRESSION IN HUMAN CULTURED CHORIONIC VILLOUSEXPLANTS

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    Objectives: Macrophage Migration Inhibitory Factor (MIF) is a cytokine originally identified for its capacity to inhibit the random migration of macrophages in vitro. MIF is a key regulator of the inflammatory and immune responses. We recently demonstrated that MIF is abundantly expressed in first trimester human trophoblast, maximal at 7-10 weeks, but declined at 11-12 weeks and remained stable until term. Since reports on mice have shown that Estrogens play an important role of macrophage MIF, we investigated the relation of Estrogens and MIF in human placenta. Methods: Chorionic villous explants were exposed to medium containing 17b-Estradiol at concentrations varying from 10-5 to 10-12 M or vehicle alone (DMSO 0.1%). At predetermined times (24, 48, 72 hours) tissues supernatants were collected and assayed by ELISA for MIF. Tissues were frozen or fixed in formalin for assaying MIF expression by western blot analysis, real time PCR and immunohistochemistry. Results: We found that while MIF release is significantly reduced in Estrogens-treated cultures in a dose-dependent manner, no changes were observed in tissues protein and mRNA content. Conclusions: Given the pro-inflammatory role of MIF, the findings suggest that down regulation of MIF secretion by Estrogens could be an important mechanism to preclude excessive inflammation in pregnancy

    17 beta - Estradiol modulates the macrophage migration inhibitory factor secretory pathway by regulation ABCA1 expression in human first - trimester placenta

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    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

    Estrogens regulate the release of Macrophage Migration Inhibitory Factor (MIF) by human chorionic villous explants

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    Aim: hormonal and cytokines factors acting locally at the maternal fetal interface are believed to play a major role in establishing the immune privilege of pregnancy. Numerous studies suggest that estrogens directly affect cellular function including cytokines production. Macrophage Migration Inhibitory Factor (MIF) is a key regulator of the inflammatory and immune responses. We recently demonstrated that MIF is abundantly expressed in first trimester human trophoblast, declined at 11-12 weeks remaining stable until term. Since reports on mice have shown that Estrogens play an important role of macrophage MIF, we investigated the link between Estrogens and the cytokine MIF in human placenta. Methods: chorionic villous explants were exposed to medium containing 17-Estradiol (E2) at concentrations varying from 10-5 to 10-12 M or vehicle alone (Ethanol 0.1%). At 6, 24, 48, hours, tissues supernatants were collected and assayed by ELISA for MIF. Tissues were frozen for assaying MIF expression by western blot analysis and real time PCR. Results: while physiological levels of E2 stimulated MIF release by chorionic villous explans, at higher concentration E2 significantly reduced MIF release in a time dependent manner. No changes were observed in tissues protein and mRNA content. Conclusion: given the crucial role of MIF as potent immunomodulator these findings suggest that Estrogens could play an important role in regulating the levels of released -MIF by the placental site
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