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BACKGROUND: Cyclosporin A (CsA) is a powerful immunosuppressive that has been widely used to prevent organ rejection and to treat certain autoimmune diseases. Our previous study showed that CsA at low concentrations could promote proliferation and invasion, and inhibit apoptosis, of human first trimester trophoblasts. In the present study, we further explored the potential mechanism and signal pathway. [ABSTRACT FROM PUBLISHER]

BACKGROUND The CC chemokines, regulated on activation, normal T-cell expressed and secreted (RANTES) and macrophage-inflammatory protein-1alpha (MIP-1α), have been identified as potential contributors to the pathogenesis and the progression of endometriosis. Dioxin, an air pollutant, and estrogen also appear to be involved in endometriosis. The aim of this study was to probe into the effect of dioxin and estrogen on expression of the chemokines in endometriosis-associated cells, and to explore the pathogenesis of endometriosis. METHODS Co-culture models were established to evaluate the secretion of human RANTES and MIP-1α. The effects of a dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and estrogen on the invasion of endometrial stromal cells (ESC) were also examined by using an invasion assay, and the translation and proteolytic activity of matrix metalloproteinase (MMP)-9 and MMP-2 in ESC were determined by western blot and zymography, respectively. RESULTS Our results showed that the combination of 17β-estradiol and TCDD increased the secretion of RANTES and MIP-1α, promoted the invasiveness of ESC and increased the expression of MMP-2 and MMP-9 in ESC. Anti-RANTES, anti-MIP-1α neutralizing antibody or antibody against their receptors could effectively inhibit the invasiveness of ESC and the expression of MMP-2 and MMP-9. CONCLUSIONS The combination of 17β-estradiol with TCDD may facilitate the onset of endometriosis and contribute to its development by increasing the invasion of ESC mediated by CC-motif chemokines. [ABSTRACT FROM AUTHOR]

BACKGROUND Decidua is in close contact with the fetal trophoblasts, and involved in immune relationship of mother to fetus. However, the roles of decidua and decidual stromal cells (DSC) in materno-fetal immune regulation remain to be elucidated. In the present study, the expression and regulation of chemokines and their receptors in decidua and DSCs were investigated. METHODS AND RESULTS The transcription of 18 chemokine receptors in human first-trimester decidual tissue and DSC were first analysed by RT-PCR. Among these receptors, C-C motif chemokine receptor-2 (CCR2) was highly transcribed. It was demonstrated by RT-PCR and immunostaining that both CCR2 and its major ligand, C-C motif chemokine ligand 2 (CCL2, monocyte chemoattractant protein-1), were expressed in decidua and DSC. We then detected CCL2 in the supernatant of primary cultures of DSC by enzyme-linked immunosorbent assay. It was shown that DSC secreted CCL2 spontaneously and continuously over 72 h (21.72 ± 2.34 ng/ml), and the CCR2 antagonist RS102895 and an inhibitor of the map kinase kinase/mitogen-activated protein kinase (ERK/MAPK) signal pathway decreased significantly the CCL2 secretion of DSC (both P CONCLUSIONS CCR2 and CCL2 are co-expressed by human first-trimester DSC and decidual tissue. CCL2 is secreted in an autocrine manner through the ERK/MAPK pathway, and is up-regulated by the pregnancy-associated hormones, estrogen, progesterone and HCG, which suggests that CCL2 may play an important role at materno-fetal interface. [ABSTRACT FROM AUTHOR]

BACKGROUND Cyclosporin A (CsA) is an immunosuppressent which is used for preventing allograft rejection. Little is known, however, about the effect of CsA on the materno–fetal relationship. Our aim was to probe into the effect of CsA on the invasiveness of human first-trimester trophoblast cells and explore possible molecules involved, with a view to providing a new therapeutic approach for pregnancy complications with trophoblast disorder. METHODS The effects of CsA on invasion of the first-trimester human trophoblasts were examined by matrigel invasion assay, and the transcription, translation and proteolytic activity of matrix metalloproteinase (MMP-9) and MMP-2 in these cells were estimated by RT-PCR, in-cell Western and zymography, respectively. The phosphorylation level of extracellular-signal related kinase (ERK) 1/2 in trophoblasts induced by CsA was also evaluated by in-cell Western. RESULTS CsA increased the invasive index of first-trimester human trophoblasts (P P P CONCLUSIONS CsA improves the invasiveness and activity of MMP 9 and MMP 2 in vitro of the first-trimester human trophoblast cells through activation of mitogen-activated protein kinase/extracellular-signal related kinase (ERK) 1/2 signaling pathway, which suggests this drug has a favorable modulation on the function of human first-trimester trophoblast cells. [ABSTRACT FROM AUTHOR]