Interleukin‐6 Activates Signal Transducer and Activator of Transcription and Mitogen‐Activated Protein Kinase Signal Transduction Pathways and Induces De Novo Protein Synthesis in Human Neuronal Cells

• Published in: Journal of neurochemistry Vol. 73; no. 5; pp. 2009 - 2017
• Main Authors: SCHUMANN, G, HUELL, M, MACHEIN, U, HOCKE, G, FIEBICH, B. L
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.11.1999; Blackwell
• Subjects: Animals; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dimerization; DNA-Binding Proteins - metabolism; Hippocampus - metabolism; Humans; Interleukin-6 - pharmacology; Medical sciences; Mitogen-Activated Protein Kinases - metabolism; Nerve Tissue Proteins - biosynthesis; Neuroblastoma; Neurology; Neurons - metabolism; Phosphorylation; Phosphoserine - metabolism; Phosphotyrosine - metabolism; Rats; Signal Transduction; STAT1 Transcription Factor; STAT3 protein; STAT3 Transcription Factor; Trans-Activators - metabolism; Tumor Cells, Cultured; Human; Nervous system diseases; Transcription; Enzyme; Alzheimer disease; Transferases; Cytokine; Biosynthesis; Cerebral disorder; Interleukin 6; Signal transduction; Acute phase protein; Cell line; Protein kinase; Central nervous system disease; Degenerative disease
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1999.02009.x

Interleukin-6 (IL-6) is involved in the pathophysiology of various diseases of the CNS. Because the molecular mechanism of action of this cytokine in human neurons is not well understood, we were interested in characterizing and defining a model system for IL-6-induced activation of signal transduction cascades, transcriptional activation, and protein synthesis in human neuronal cells. We show that IL-6 leads to transcriptional activation of signal transducer and activator of transcription 3 (STAT3) in human SH-SY5Y neuroblastoma cells. IL-6-induced activation and translocation of STAT3 and to a lesser degree STAT1 but not STAT5 are demonstrated. STAT3 is phosphorylated on Tyr705 and Ser727 residues on stimulation with IL-6, suggesting maximal activation of transcription. We also show IL-6-induced phosphorylation of p42/44 mitogen-activated protein (MAP) kinase, providing evidence for MAP kinase pathway activation. The physiological relevance of our results is confirmed by IL-6-induced phosphorylation of key signaling proteins of both STAT and MAP kinase pathway in rat primary hippocampal neurons. Furthermore, de novo protein synthesis on IL-6 activation is demonstrated.