PMID- 10537060 OWN - NLM STAT- MEDLINE DCOM- 19991105 LR - 20091119 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 73 IP - 5 DP - 1999 Nov TI - 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. PG - 2009-17 AB - 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. FAU - Schumann, G AU - Schumann G AD - Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Germany. FAU - Huell, M AU - Huell M FAU - Machein, U AU - Machein U FAU - Hocke, G AU - Hocke G FAU - Fiebich, B L AU - Fiebich BL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (DNA-Binding Proteins) RN - 0 (Interleukin-6) RN - 0 (Nerve Tissue Proteins) RN - 0 (STAT1 Transcription Factor) RN - 0 (STAT1 protein, human) RN - 0 (STAT3 Transcription Factor) RN - 0 (STAT3 protein, human) RN - 0 (Stat1 protein, rat) RN - 0 (Stat3 protein, rat) RN - 0 (Trans-Activators) RN - 17885-08-4 (Phosphoserine) RN - 21820-51-9 (Phosphotyrosine) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - DNA-Binding Proteins/*metabolism MH - Dimerization MH - Hippocampus/metabolism MH - Humans MH - Interleukin-6/*pharmacology MH - Mitogen-Activated Protein Kinases/*metabolism MH - Nerve Tissue Proteins/*biosynthesis MH - Neuroblastoma MH - Neurons/*metabolism MH - Phosphorylation MH - Phosphoserine/metabolism MH - Phosphotyrosine/metabolism MH - Rats MH - STAT1 Transcription Factor MH - STAT3 Transcription Factor MH - *Signal Transduction MH - Trans-Activators/*metabolism MH - Tumor Cells, Cultured EDAT- 1999/10/28 00:00 MHDA- 1999/10/28 00:01 CRDT- 1999/10/28 00:00 PHST- 1999/10/28 00:00 [pubmed] PHST- 1999/10/28 00:01 [medline] PHST- 1999/10/28 00:00 [entrez] PST - ppublish SO - J Neurochem. 1999 Nov;73(5):2009-17.