The granulocyte colony stimulating factor (G-CSF) activates Jak/STAT and MAPK pathways in a trophoblastic cell line.
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.
Marino
Verónica Julieta
VJ
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.
Roguin
Leonor Patricia
LP
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D053613:Janus Kinase 1 / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor / Q000378:metabolism; D053634:TYK2 Kinase / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016179:Granulocyte Colony-Stimulating Factor; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053634:TYK2 Kinase; C070139:TYK2 protein, human; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases