The granulocyte colony stimulating factor (G‐CSF) activates Jak/STAT and MAPK pathways in a trophoblastic cell line

Abstract Granulocyte colony‐stimulating factor receptor (G‐CSFR) has been found in placenta tissues, although its functional role has not yet been defined. In order to explore the molecular pathways induced by G‐CSF in this tissue, we first reveal the presence of G‐CSFR in the JEG‐3 human trophoblastic cell line and then examined the phosphorylation of Janus tyrosine kinases (Jak), signal transducers and activators of transcription (STAT) proteins and mitogen‐activated protein kinases (MAPK) after G‐CSF binding to receptors. We showed that Jak1, Jak2, Tyk2, and STAT3 were phosphorylated after incubation with G‐CSF. Phosphorylation of p38 and p44/42 MAPK was also activated by G‐CSF, and specifically blocked in the presence of the corresponding inhibitors. Similar intracellular pathways were induced by G‐CSF in a myeloid leukemia NFS‐60 cell line that was studied in parallel. Conversely to cytokine action in myeloid cells, G‐CSF did not induce a proliferative response in JEG‐3 cells. When the effect of G‐CSF on cellular viability was evaluated, cytokine‐stimulated JEG‐3 cells were protected from foetal serum starvation. In addition, when JEG‐3 cells deprived of serum were incubated at different times in the presence of G‐CSF, a progressive decrease in the percentage of hypodiploid cells was observed. In summary, we identified the molecular pathways activated after G‐CSF binding to trophoblastic cell receptors and showed that G‐CSF behaved as a protective cytokine, which supports JEG‐3 cells survival. J. Cell. Biochem. 103: 1512–1523, 2008. © 2007 Wiley‐Liss, Inc.