Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
PLoS One. 2012;7(7):e41033. doi: 10.1371/journal.pone.0041033. Epub 2012 Jul 27.

Toll-like signaling and the cytokine IL-6 regulate histone deacetylase dependent neuronal survival.

Author information

  • 1Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.

Abstract

Histone deacetylase (HDAC) proteins have a role in promoting neuronal survival in vitro, but the mechanism underlying this function has not been identified. Here we provide evidence that components of the neuronal microenvironment, including non-neuronal cells and defined culture media, can mitigate midbrain neuronal cell death induced by HDAC inhibitor treatment. Using microarrays we further identified gene expression changes taking place in non-neuronal cells as a result of HDAC inhibition. This analysis demonstrated that HDAC inhibitor treatment results in the down-regulation of immunity related signaling factors, in particular the Toll-like receptors (TLR). TLR signaling is active in cultured midbrain cells, yet blocking TLR receptors is not sufficient to cause neuronal cell death. In contrast, selective activation of this pathway using TLR ligands can modestly block the effects of HDAC inhibition. Furthermore, we observed that the negative effects of HDAC inhibitor treatment on neuronal survival could be more substantially blocked by the cytokine Interleukin-6 (IL-6), which is a major downstream target of TLR signaling. These data suggest that HDACs function to promote neuronal survival by activating a TLR and IL-6 dependent pathway.

PMID:
22848425
[PubMed - indexed for MEDLINE]
PMCID:
PMC3407143
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk