title: Signal transduction pathways of GM-CSF in neural cell lines.
abstract: GM-CSF is recently being suggested to play important role(s) in the nervous system. Present study was intended to understand signal transduction pathways of GM-CSF in human neuroblastoma (SK-N-(BE)2) and glioblastoma (A172) cell lines. The expression of GM-CSF receptors on the surface of these cells was confirmed by immunocytochemistry, Western blot analysis and RT-PCR. When treated for 10min, GM-CSF activated the signal transducer and activator of transcription 5 (STAT5) and extracellular signal regulated kinase (ERK) in both cell lines. However, Janus kinase 2 (JAK2) was activated only in A172 cells but not in SK-N-(BE)2 cells by GM-CSF. The GM-CSF-activated cellular signal pathways were specifically inhibited by the pretreatment of GM-CSF receptor alpha antibody, suggesting the specificity of the signal activation. The experiment using specific inhibitors (AG490) to the JAK/STAT pathway showed that JAK2/STAT5 cascade was well preserved and activated by GM-CSF in A172 cells, while STAT5 was activated by GM-CSF without JAK2 activation in SK-N-(EB)2 cells. The ERK pathway was activated by GM-CSF independently of JAK2 in both cell lines. Finally, GM-CSF showed cytoprotective effect on these cell lines by inhibiting cytotoxicity of saturosporine. The results revealed the signal transduction pathways activated by GM-CSF in neural cells and suggested that GM-CSF might affect the neural functions via these signal pathways.
authors.affiliation: Inha Neural Repair Center, Inha University Hospital, Inha University College of Medicine, Incheon, Republic of Korea.
authors.forename: Jung Kyoung
authors.initials: JK
authors.lastname: Choi
authors.forename: Byung Hyune
authors.initials: BH
authors.lastname: Choi
authors.forename: Yoon
authors.initials: Y
authors.lastname: Ha
authors.forename: Hyeonseon
authors.initials: H
authors.lastname: Park
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Yoon
authors.forename: Hyung Chun
authors.initials: HC
authors.lastname: Park
authors.forename: So Ra
authors.initials: SR
authors.lastname: Park
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D011247:Pregnancy; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D013234:Stem Cells / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D050799:STAT5 Transcription Factor; D012313:RNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007770:L-Lactate Dehydrogenase; D053614:Janus Kinase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D019311:Staurosporine