Peer-Reviewed Journal Details
Mandatory Fields
Green, HF,Nolan, YM
2012
January
Neurochemistry International
GSK-3 mediates the release of IL-1 beta, TNF-alpha and IL-10 from cortical glia
Validated
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Optional Fields
GSK-3 Lithium Glia Cytokine beta-Catenin Lipopolysaccharide GLYCOGEN-SYNTHASE KINASE-3 ALZHEIMERS-DISEASE LITHIUM INFLAMMATION
61
666
671
Neuroinflammation has been shown to contribute to neurodegenerative and psychiatric disorders such as Alzheimer's disease and major depression due to the inappropriate release of pro-inflammatory cytokines from activated microglia. The precise molecular events that mediate cytokine release from glia remain unknown but we suggest that the serine/threonine kinase glycogen synthase kinase-3 (GSK-3) may be involved. The aim of this study therefore was to investigate the effect of lipopolysaccharide (LPS) on expression and activity of the GSK-3 beta isoform in glia, and to assess if GSK-3 mediates the LPS-induced change in inflammatory cytokine levels in culture medium from rat glial-enriched cortical cultures. GSK-3 beta was expressed in microglia and astrocytes, and stimulation of these cultures with LPS induced an increase in GSK-3 beta expression and activity, and in pro-inflammatory cytokine levels in culture media. We show that GSK-3 inhibition using a small molecule inhibitor SB216763 or the mood stabiliser lithium chloride reduced the LPS-induced elevated levels of pro-inflammatory cytokines present in culture media from rat glial-enriched cortical cultures. These results demonstrate a role for GSK-3 as a modulator of inflammatory cytokine levels in the brain, and contribute to a mechanistic insight into neurological disorders in which neuroinflammation is a characteristic feature. (C) 2012 Elsevier Ltd. All rights reserved.
DOI 10.1016/j.neuint.2012.07.003
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