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including Psychoneuroimmunology, Neuro
Reproductive Medicine, Chronobiology
and Human Ethology
ISSN 0172–780X

NEL Vol.23 No.4, August 2002


2002; 23:239-242
pii: NEL230302A06
PMID: 12195235

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The effects of interleukin-6, leukemia inhibitory factor and interferon-gamma on STAT DNA binding and c-fos mRNA levels in cortical astrocytes and C6 glioma cells
Shirzad Jenab & Vanya Quinones-Jenab

Department of Psychology, Hunter College of City University of New York, 695 Park Avenue, New York, NY 10021, USA.

Key words:
astrocyte; C6 glioma; c-fos; STAT; IL-6; IFN-g; LIF

Submitted: Aptil 2, 2002
Accepted: June 5, 2002


OBJECTIVES: The purpose of this study was to compare the effects of neurotrophic cytokines on the JAK/STAT transcription factors and the immediate early gene, c-fos, in C6 glioma cells and in primary astrocyte cultures.

METHODS: In this study we compared the effects of interleukin 6, leukemia inhibitory factor and interferon gamma on C6 glioma cells and on primary astrocyte cultures using electrophoretic mobility shift assay and quantitative solution hybridization/Northern Blot analysis.

RESULTS: We show that interleukin 6, leukemia inhibitory factor and interferon gamma treatment induce the nuclear STAT3 and STAT1 proteins to bind to the sis inducible element of c-fos in both C6 glioma cells and primary cortical astrocytes. Furthermore, quantitative solution hybridization and Northern blot analysis show the differential regulation of c-fos mRNA levels by interleukin-6 (8.1 and 4.0 folds) and leukemia inhibitory factor (5.4 and 3.2 folds) in C6 and astrocyte cultures (respectively). However, interferon gamma increases in c-fos mRNA levels (2.9 fold in both C6 and astrocyte cultures) were not significant in a one way ANOVA.

CONCLUSION: This study suggests that two initial cytokine signaling pathways are present and functional in C6 glioma cells and in primary astrocyte cultures.


Interleukin 6 (IL-6) and Leukemia inhibitory factor (LIF), are multifunctional members of the gp130 cytokine family, that include oncostatin M (OSM), and ciliary neurotrophic factor (CNTF). These cytokines are synthesized by a variety of cells and have broad range of biological activities, that include stimulation of acute-phase proteins in hepatocytes, hematopoietic cell development, and regulation of neuronal and astrocytic development, differentiation, and inflammation [1–6]. Through the activation of JAK/STAT proteins in neuroblastoma cell lines, in primary hippocampal neurons, in sympathetic ganglia, and following transient ischemia in cortex and striatum astrocytes [7–11], these cytokines regulate the expression of many genes, including c-fos, jun B, opioid peptides and receptors, neuropeptides, and nitric oxide synthase [12–20]. In this study we compare the effects of IL-6, LIF and interferon gamma (IFN-g) on activation of a functional JAK/STAT/c-fos signaling pathway in C6 glioma cell line and in primary cortical astrocyte cultures.

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