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 < 0.01), as well as the messenger RNA, protein levels (both P < 0.01) and proteolytic activity (P < 0.05) of MMP-9 and MMP-U0126, a mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor, inhibited the enhanced invasiveness and activity of MMP-9 and MMP-in these cells induced by CsA. In addition, CsA activated the ERK1/2 in a time-dependent manner. 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.
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 < 0.01), as well as the messenger RNA, protein levels (both P < 0.01) and proteolytic activity (P < 0.05) of MMP-9 and MMP-U0126, a mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor, inhibited the enhanced invasiveness and activity of MMP-9 and MMP-in these cells induced by CsA. In addition, CsA activated the ERK1/2 in a time-dependent manner. 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.
Authors: Francesco Franceschi; Nicoletta Di Simone; Silvia D'Ippolito; Roberta Castellani; Fiorella Di Nicuolo; Giovanni Gasbarrini; Yoshio Yamaoka; Tullia Todros; Giovanni Scambia; Antonio Gasbarrini Journal: Helicobacter Date: 2012-06-29 Impact factor: 5.753