Human PSG1a induces, directly and through the induction of Th17 cells, the proangiogenic factors IL-6 and VEGF in JEG-3 choriocarcinoma cell line

MARTINEZ, FERNANDO; KNUBEL, C; MOTRAN, CLAUDIA C

Mar del Plata

Congreso; LVII Reunión Científica Anual de la Sociedad Argentina de Inmunologia y LVI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica.; 2009

SAI. SAIC

Human PSG1a induces, directly and through the induction of Th17 cells, the proangiogenic factors IL-6 and VEGF in JEG-3 choriocarcinoma cell line.   Fernando F. Martínez, Carolina P. Knubel and Claudia C Motran. Clinical Biochemical Department. CIBICI-CONICET. Chemical Sciences Faculty. National University of Cordoba.   Trophoblast cells display an exceptional capability: they physiologically invade into the surrounding tissue. This capability is widely associated with tumours, and, indeed, the invasive behaviour of both is rather similar.  The proangiogenic factors IL-6, TGF-b and vascular endothelial growth factor (VEGF) have been implicated in the process of proper placental development.  Besides, recently IL-17 has been shown to induce neovascularization and the production of proangiogenic molecules in tumours through an IL-6-Stat-3 signalling pathway.  Pregnancy-specific glycoproteins (PSG) are a family of highly similar proteins synthesized in large amounts by the placental syncytiotrophoblast.  We have demonstrated that PSG1a, the major variant of PSG polypeptides, has immunoregulatory functions due to her ability to modulate macrophages and dendritic cells (DC) cytokine secretion. Treatment of murine DC with recombinant PSG1a induces IL-6 and TGF-b secretion.  In addition, during an in vitro OVA peptide-restricted assay, PSG1a-treated DC exhibit a capacity to prime CD4+ T cells from DO11.10 transgenic mice to produce IL-4, IL-5, IL-10 and IL-17.  The aim of this work was to investigate whether PSG1a as well as IL-17 can modulate the IL-6-Stat-3 proangiogenic pathway in trophoblast cells.  Human PSG1a as well as human IL-17 were able to induce IL-6 secretion and STAT-3 phosphorylation in Jeg-3 cells, although they did Stat-3 activation with significantly different kinetics (1 h for PSG1a and 6 h for IL-17). Similarly, we found that PSG1a and IL-17 induced VEGF up-regulation at 6 and 24 h respectively. In addition, levels of PSG1a and IL-17 positively correlated with IL-6 secretion, Stat3 activity and VEGF expression in trophoblast cells. PSG1a can thus promote, directly and through the induction of Th17 cells, trophoblast invasion