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

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.