NEUROENDOCRINOLOGY
LETTERS including Psychoneuroimmunology, Neuropsychopharmacology,
Reproductive Medicine, Chronobiology
and
Human Ethology
ISSN 0172–780X
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.
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.
Introduction
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.
