Spatiotemporal patterns of macrophage migration inhibitory factor (Mif) expression in the mouse placenta
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RESEARCH
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Spatiotemporal patterns of macrophage migration inhibitory factor (Mif) expression in the mouse placenta Miriam R Faria1, Mara S Hoshida1, Eloisa AV Ferro2, Francesca Ietta3, Luana Paulesu3, Estela Bevilacqua1*
Abstract Background: Macrophage migration inhibitory factor (MIF) has special pro-inflammatory roles, affecting the functions of macrophages and lymphocytes and counter-regulating the effects of glucocorticoids on the immune response. The conspicuous expression of MIF during human implantation and early embryonic development also suggests this factor acts in reproductive functions. The overall goal of this study was to evaluate Mif expression by trophoblast and embryo placental cells during mouse pregnancy. Methods: Mif was immunolocalized at implantation sites on gestation days (gd) 7.5, 10.5, 13.5 and 17.5. Ectoplacental cones and fetal placentas dissected from the maternal tissues were used for Western blotting and qRT-PCR assays on the same gestation days. Results: During the post-implantation period (gd7.5), trophoblast giant cells showed strong Mif reactivity. In later placentation phases (gds 10.5-17.5), Mif appeared to be concentrated in the junctional zone and trophoblast giant cells. Mif protein expression increased significantly from gd7.5 to 10.5 (p = 0.005) and from gd7.5 to 13.5 (p = 0.03), remaining at high concentration as gestation proceeded. Higher mRNA expression was found on gd10.5 and was significantly different from gd13.5 (p = 0.048) and 17.5 (p = 0.009). Conclusions: The up-regulation of Mif on gd10.5 coincides with the stage in which the placenta assumes its three-layered organization (giant cells, spongiotrophoblast and labyrinth zones), fetal blood circulation begins and population of uNK cells reaches high proportions at the maternal counter part of the placenta, suggesting that Mif may play a role in either the placentation or in the adaptation of the differentiated placenta to the uterus or still in gestational immunomodulatory responses. Moreover, it reinforces the possibility of specific activities for Mif at the maternal fetal interface.
Background Macrophage migration inhibitory factor (MIF) is a widely-expressed pleiotropic cytokine, exhibiting a broad range of roles that include pro-inflammatory activities in innate and acquired immunity, glucocorticoid antagonism [1-5], cell proliferation and survival [6-8], cell migration [9,10], modulation of NK-associated immune responses [11], DNA damage response and proteasomal control of the cell cycle [12]. It is constitutively expressed by a wide variety of cells [2,13] and can be
* Correspondence: [email protected] 1 Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil Full list of author information is available at the end of the article
either continuously expressed and secreted or stored intracellularly [2]. MIF has been particularly studied during an inflammatory response. Cytokines such as tumor necrosis factoralpha (TNF-a) and interferon-gamma (IFN-g) induce MIF expression by
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