Induction of interleukin-6 by depolarization of neurons
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 regula...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
December 1, 2000
|
| In: |
The journal of neuroscience
Year: 2000, Volume: 20, Issue: 23, Pages: 8637-8642 |
| ISSN: | 1529-2401 |
| DOI: | 10.1523/JNEUROSCI.20-23-08637.2000 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1523/JNEUROSCI.20-23-08637.2000 Verlag, lizenzpflichtig, Volltext: https://www.jneurosci.org/content/20/23/8637 
|
| Author Notes: | Svea Sallmann, Eric Jüttler, Simone Prinz, Nicole Petersen, Udo Knopf, Thomas Weiser, and Markus Schwaninger |
| Summary: | 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. |
|---|---|
| Item Description: | Gesehen am 01.04.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1529-2401 |
| DOI: | 10.1523/JNEUROSCI.20-23-08637.2000 |