Linked Life Data

11102468

Source:http://linkedlifedata.com/resource/pubmed/id/11102468

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2001-1-4
pubmed:abstractText
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 Ca(2+) levels or by inhibiting L-type Ca(2+) channels or Ca(2+)/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 Ca(2+)-responsive promoter element. Through this mechanism, IL-6 may function as a neuromodulator induced by neuronal activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8637-42
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11102468-Animals, pubmed-meshheading:11102468-Calcium, pubmed-meshheading:11102468-Calcium Channel Blockers, pubmed-meshheading:11102468-Calcium Channels, L-Type, pubmed-meshheading:11102468-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:11102468-Cell Membrane, pubmed-meshheading:11102468-Cells, Cultured, pubmed-meshheading:11102468-Dexamethasone, pubmed-meshheading:11102468-Extracellular Space, pubmed-meshheading:11102468-Gene Expression Regulation, pubmed-meshheading:11102468-Genes, Reporter, pubmed-meshheading:11102468-Interleukin-6, pubmed-meshheading:11102468-Male, pubmed-meshheading:11102468-Mice, pubmed-meshheading:11102468-Mutagenesis, Site-Directed, pubmed-meshheading:11102468-Neurons, pubmed-meshheading:11102468-PC12 Cells, pubmed-meshheading:11102468-Potassium, pubmed-meshheading:11102468-Promoter Regions, Genetic, pubmed-meshheading:11102468-RNA, Messenger, pubmed-meshheading:11102468-Rats, pubmed-meshheading:11102468-Receptors, Glucocorticoid, pubmed-meshheading:11102468-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:11102468-Transcription, Genetic, pubmed-meshheading:11102468-Transfection
pubmed:year
2000
pubmed:articleTitle
Induction of interleukin-6 by depolarization of neurons.
pubmed:affiliation
Department of Neurology, University of Heidelberg, 69120 Heidelberg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't