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

J Cell Biochem. 2008 Apr 1;103(5):1512-23. doi: 10.1002/jcb.21542.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Humans
  • Janus Kinase 1 / metabolism
  • Janus Kinase 2 / metabolism
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / physiology
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Receptors, Granulocyte Colony-Stimulating Factor / metabolism
  • Recombinant Proteins
  • STAT3 Transcription Factor / metabolism
  • TYK2 Kinase / metabolism
  • Trophoblasts / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Receptors, Granulocyte Colony-Stimulating Factor
  • Recombinant Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Granulocyte Colony-Stimulating Factor
  • JAK1 protein, human
  • JAK2 protein, human
  • Janus Kinase 1
  • Janus Kinase 2
  • TYK2 Kinase
  • TYK2 protein, human
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases