Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-8-22
pubmed:abstractText
No therapy currently exists to repair demyelinated lesions in multiple sclerosis. However, the use of IgM antibodies may provide a valuable therapeutic avenue for evoking such repair. Unfortunately, the mechanism of immunoglobulin action in CNS repair is currently unknown but may depend upon complex interactions between multiple cell types rather than upon direct activation of a single cell type. Using rat mixed glial cultures containing oligodendrocytes, microglia, and astrocytes, we found that the Fc portion of human IgM shifts microglia to an activated phenotype, reduces glial proliferation, upregulates a variety of immediate early genes, including JunB, Egr-1, and c-Fos, and stimulates microglial production and release of IL-1beta. Microglia-derived IL-1beta consequently triggers transcriptional upregulation of immediate early genes such as c-Jun, Egr-1, and c-Fos in the mixed glial cultures, and stimulates the upregulation of late response genes such as lipocalin in purified oligodendrocytes. Treatment with an IL-1beta receptor antagonist abrogates the effects of Fcmu on glial proliferation and prevents the upregulation of lipocalin in response to Fcmu, but does not prevent Fcmu-mediated upregulation of IL-1beta, suggesting that IL-1beta mediates at least some of the downstream effects of Fcmu in mixed glial cultures. We hypothesize that Fcmu-stimulated IL-1beta-induced upregulation of immediate early and late response genes in oligodendrocytes may promote CNS repair.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0969-9961
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
731-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16887357-Animals, pubmed-meshheading:16887357-Animals, Newborn, pubmed-meshheading:16887357-Carrier Proteins, pubmed-meshheading:16887357-Cell Communication, pubmed-meshheading:16887357-Cells, Cultured, pubmed-meshheading:16887357-Coculture Techniques, pubmed-meshheading:16887357-Female, pubmed-meshheading:16887357-Gene Expression Regulation, pubmed-meshheading:16887357-Genes, Immediate-Early, pubmed-meshheading:16887357-Immunologic Factors, pubmed-meshheading:16887357-Interleukin-1, pubmed-meshheading:16887357-Lipocalin 1, pubmed-meshheading:16887357-Microglia, pubmed-meshheading:16887357-Multiple Sclerosis, pubmed-meshheading:16887357-Myelin Sheath, pubmed-meshheading:16887357-Nerve Regeneration, pubmed-meshheading:16887357-Oligodendroglia, pubmed-meshheading:16887357-Phenotype, pubmed-meshheading:16887357-Rats, pubmed-meshheading:16887357-Rats, Sprague-Dawley, pubmed-meshheading:16887357-Receptors, Fc, pubmed-meshheading:16887357-Receptors, Interleukin-1, pubmed-meshheading:16887357-Transcriptional Activation, pubmed-meshheading:16887357-Up-Regulation
pubmed:year
2006
pubmed:articleTitle
Activated microglia stimulate transcriptional changes in primary oligodendrocytes via IL-1beta.
pubmed:affiliation
Department of Neuroscience, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. howe.charles@mayo.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural