Induction of interleukin-6 by depolarization of neurons

• Verfasst von: Sallmann, Svea [VerfasserIn]
• Verfasst von: Jüttler, Eric [VerfasserIn]
• Verfasst von: Prinz, Simone [VerfasserIn]
• Verfasst von: Petersen, Nicole [VerfasserIn]
• Verfasst von: Knopf, Udo [VerfasserIn]
• Verfasst von: Weiser, Thomas [VerfasserIn]
• Verfasst von: Schwaninger, Markus [VerfasserIn]
• Titel: Induction of interleukin-6 by depolarization of neurons
• Verf.angabe: Svea Sallmann, Eric Jüttler, Simone Prinz, Nicole Petersen, Udo Knopf, Thomas Weiser, and Markus Schwaninger
• E-Jahr: 2000
• Jahr: December 1, 2000
• Umfang: 6 S.
• Teil: volume:20
• Teil: year:2000
• Teil: number:23
• Teil: pages:8637-8642
• Teil: extent:6
• Fussnoten: Gesehen am 01.04.2021
• Titel Quelle: Enthalten in: The journal of neuroscience
• Ort Quelle: Washington, DC : Soc., 1981
• Jahr Quelle: 2000
• Band/Heft Quelle: 20(2000), 23, Seite 8637-8642
• ISSN Quelle: 1529-2401
• DOI: doi:10.1523/JNEUROSCI.20-23-08637.2000
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: calcium
• Sach-SW: cytokine
• Sach-SW: gene transcription
• Sach-SW: IL-6
• Sach-SW: membrane depolarization
• Sach-SW: neurons
• K10plus-PPN: 1753076676

Abstract

Interleukin-6 (IL-6) has neuromodulatory and neuroprotective effects in vivo. It is expressed in glial cells and neurons both under physiological conditions and in various neurological diseases. Although the expression of IL-6 in glia has been intensely investigated, little is known about the regulation of IL-6 production by neurons. Therefore, we investigated the regulation of IL-6 expression in neurons. Membrane depolarization raised IL-6 mRNA accumulation in primary cortical cells and the PC-12 cell line.In vivo, IL-6 mRNA in the brain increased significantly after epileptic seizures. To investigate IL-6 gene transcription, PC-12 cells were transfected with reporter gene constructs containing the human IL-6 promoter. Membrane depolarization raised IL-6 transcription twofold to fourfold. This increase could be blocked by lowering extracellular Ca2+ levels or by inhibiting L-type Ca2+ channels or Ca2+/calmodulin-dependent protein kinases. Internal mutations in various elements of the IL-6 promoter revealed the glucocorticoid response element (GRE) 2 to be a depolarization-responsive element. Although the GRE2 bound the glucocorticoid receptor (GR) and was stimulated by dexamethasone, the GR was not responsible for the effect of membrane depolarization because a consensus GRE did not mediate stimulation by membrane depolarization. Instead, another yet undefined factor that binds to the IL-6 GRE2 may mediate the response to membrane depolarization. These data demonstrate that the expression of IL-6 in neurons is regulated by membrane depolarization and suggest a novel Ca2+-responsive promoter element. Through this mechanism, IL-6 may function as a neuromodulator induced by neuronal activity.