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.

• Authors: Verónica Julieta Marino, Leonor Patricia Roguin
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 103 Issue 5 Pg. 1512-23 (Apr 01 2008) ISSN: 1097-4644 [Electronic] United States
• PMID: 17879956 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2007 Wiley-Liss, Inc.

Chemical References

• 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

Topics

• Cell Line, Tumor
• Cell Survival (drug effects, physiology)
• Granulocyte Colony-Stimulating Factor (pharmacology)
• Humans
• Janus Kinase 1 (metabolism)
• Janus Kinase 2 (metabolism)
• MAP Kinase Signaling System (drug effects, 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)