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Glioblastoma multiforme (GBM) is the most common and malignant tumor in the central nervous system. One of the contemporary hypotheses postulates that its pathogenesis is associated with the cancer stem cells (CSCs) which originate from mutations in the normal neural stem cells residing in their specific "niches." Simultaneously with its aggressive development the tumor suppresses the local immune system by different secreted and/or cell expressed factors. Progesterone-induced blocking factor (PIBF) is an immunomodulatory protein with known role in the regulation of the immune response in the reproductive system. Expression of PIBF has been described in some tumors as one of the factors suppressing the anti-tumor immunity. The aim of the present study was to check for the expression of PIBF from cells isolated from six GBMs. To characterize the cultured cells and to study the PIBF expression confocal microscopy, flow cytometry, ELISA, and real-time PCR were used. The results obtained showed expression of markers typical for cancer CSCs and secretion of interleukin 6 by the GBM-derived cultured cells. The results convincingly prove that PIBF is intracellularly expressed by the cultured cells from the all six GBM samples, and this fact is confirmed by three different methods-flow cytometry, confocal microscopy, and real-time PCR. This paper reports for the first time the expression of PIBF by GBM-derived cells cultured in vitro and reveals a new aspect of the immunosuppressive mechanism used by GBM in escaping the immune control.

Progesterone is considered to be a major reproductive steroid hormone which supports the successful development of pregnancy. One of the basic targets of progesterone are stromal cells in endometrium which are triggered to undergo decidualization in preparation to accept the embryo. However, the endometrial stroma consists of different subpopulations of cells with varying characteristics and functions as one of the subpopulations are the endometrial mesenchymal stem cells (MSCs) which seem to be located both in the basal layer and in the functional layer of the endometrium. In all cases, these cells have the features of typical MSCs such as adherence and differentiation in multiple cell lineages. The endometrial MSCs are stimulated by progesterone to increase the expression and secretion of immunomodulatory proteins such as HLA-G and PIBF., (Copyright © 2011 Elsevier Inc. All rights reserved.)

It is well known that the reproductive steroid hormones, particularly progesterone, in addition to its widely recognized effects on endometrial epithelial and stromal cells and spiral arteries, affect the activities of T cells and natural killer cells in the deciduas, thus inducing active immune tolerance against the fetal antigens. The immunomodulatory effects of progesterone on T cells, B cells and natural killer cells have been discussed extensively in the literature. The aim of the present review is to sum up and discuss the results from this and other laboratories of investigations on the effects of progesterone on dendritic cells and adult stem cells, which are some of the other cell populations present at the fetal-maternal interface and possibly are related to the immunoregulation during pregnancy. These cells have been shown to have a number of specific functions but their involvement in the entire process of regulation of the immune response in pregnancy is still under discussion. The present review focuses on facts showing that the progesterone is a kind of 'regulator of regulators' in the decidua, thus creating the most favourable conditions for the development of the semi-allogeneic fetus in successful pregnancy., (Copyright © 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Problem: Maternal immune response to fetal tissues is modified in such way that it favors the development of pregnancy. Human leukocyte antigen (HLA)-G, progesterone and mesenchymal stem cells (MSCs) have been identified as potent immunomodulatory agents in different experimental systems and the interactions between these three factors are studies in this paper., Method of Study: Human MSCs are isolated from human adipose tissue, bone marrow and decidua are cultured in the presence of progesterone and the expression of HLA-G is followed-up at protein and mRNA levels., Results: The MSCs cultured in the presence of progesterone express increased levels of both cell surface and cytoplasmic HLA-G when compared with the control MSCs., Conclusion: Progesterone up-regulates the expression by MSCs of HLA-G which is a major player in maintenance of the immune balance between the mother and the fetus. MSCs are newly detected targets of progesterone with well documented immunomodulatory activity.

Problem: Monocyte-derived dendritic cells (mDCs) are present in human decidua during the first month of pregnancy where they experience the effect of the increased concentration of progesterone (Pg) and estradiol (Estr). The aim of our study was to assess the effect of these reproductive hormones on the immunomodulatory role of mDCs., Methods of Study: The mDCs cultured in vitro in the presence of sex steroid hormones and characterized for their apoptosis and secretion of cytokines by flow cytometry, enzyme linked immunosorbent assay and proteome profiler kit., Results: Female sex steroid hormones enhance the life cycle of mDCs, thus increasing the maturation and apoptosis, they also increase the production of interleukin (IL)-10 and IL-27 but only Pg increases the production of IL-13 and down regulates the secretion of IL-23., Conclusion: The Pg and Estr participate in the regulation of the immune response during pregnancy by influencing apoptosis and the cytokine profile of the mDCs.

Abstract: Progesterone-induced blocking factor (PIBF) has been described as an active factor intimately involved in regulation of the immune response in pregnancy. It has been shown that PIBF biased the cytokine balance to Th2-type in pregnancy and inhibited the activity of NK cells. The biological roles of PIBF would be better defined if methods for its detection and measurement in biological fluids are available. However, so far, reliable antibodies have not been developed to be used as specific probes. A monoclonal antibody designated as MAB 3A6 was produced and characterized. MAB 3A6 reacts specifically with PIBF. It can detect this protein in biological fluids when tested by immunoblot and recognizes PIBF expressed on the surface of lymphocytes of pregnant women stimulated in vitro with progesterone. The characteristics of MAB 3A6 makes it the possible basis for development of a clinically applicable assay to assess the presence and concentration of PIBF in biological samples. [Copyright &y& Elsevier]

Problem Monocyte-derived dendritic cells (mDCs) are present in human decidua during the first month of pregnancy where they experience the effect of the increased concentration of progesterone (Pg) and estradiol (Estr). The aim of our study was to assess the effect of these reproductive hormones on the immunomodulatory role of mDCs. Methods of study The mDCs cultured in vitro in the presence of sex steroid hormones and characterized for their apoptosis and secretion of cytokines by flow cytometry, enzyme linked immunosorbent assay and proteome profiler kit. Results Female sex steroid hormones enhance the life cycle of mDCs, thus increasing the maturation and apoptosis, they also increase the production of interleukin (IL)-10 and IL-27 but only Pg increases the production of IL-13 and down regulates the secretion of IL-23. Conclusion The Pg and Estr participate in the regulation of the immune response during pregnancy by influencing apoptosis and the cytokine profile of the mDCs. [ABSTRACT FROM AUTHOR]