INVESTIGADORES
MARINO Veronica Julieta
congresos y reuniones científicas
Título:
Granulocyte colony stimulating factor activates different pathways after binding to receptors in trophoblastic cells
Autor/es:
MARINO JULIETA; ROGUIN LEONOR
Lugar:
Viena, Austria
Reunión:
Congreso; 6th Joint Meeting of Cytokines 2006, Molecular Biology & Human Diseases; 2006
Resumen:
The granulocyte colony-stimulating factor (G-CSF) is a cytokine that supports the proliferation and differentiation of myeloid precursors to neutrophils in bone marrow and activates the function of mature neutrophils. Although G-CSF functions are well known in granulocyte cell lines, receptors for this cytokine have also been found in non-haemopoietic sites, including endothelial cells, cardiomyocytes, neuronal precursors and placenta. In a previous work we identified the cytokine conformational epitope involved in binding to receptors from placenta and myeloid cells (NFS-60). In the present study, in order to explore the biological action of G-CSF in placenta, we employed the trophoblastic cell line JEG-3. We first revealed the presence of cytokine specific receptors in these cells and determined affinity constant and binding capacity values of 3x109 M-1 and 1290 sites/cell, respectively, which were similar to those obtained in NFS-60 cells. Since G-CSF binding to hematopoietic cells receptors induces signal transduction by activating the receptor-associated Janus family tyrosine kinases (Jak) and signal transducer and activator of transcription (STAT) proteins as well as the mitogen activated protein kinases (MAPK), we then examined the possible contribution of these pathways in trophoblastic cells signalling. Results showed that G-CSF induced Jak1, Jak2, Tyk-2 and STAT3, but not STAT1 and STAT5 phosphorylation in both myeloid and trophoblastic cells. Furthermore, p38 MAPK and p44/42 MAPK were also phosphorylated in a time-dependent manner. Although G-CSF induces a mitogenic response on NFS-60 cells, trophoblastic cells proliferation was not stimulated in the presence of cytokine. However, when the effect of G-CSF on cellular viability was evaluated, it was shown that cytokine-stimulated JEG-3 cells were protected from cell death induced in the absence of serum. In summary, our results represent the first report of intracellular signals triggered after G-CSF binding to receptors from placenta and suggest a functional role of G-CSF in trophoblastic cells, probably related to cell survival.