Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Astrocyte galectin-9 potentiates microglial TNF secretion.

Authors: Steelman, AJ  Li, J 
Citation: Steelman AJ and Li J, J Neuroinflammation. 2014 Aug 27;11:144. doi: 10.1186/s12974-014-0144-0.
Pubmed: (View Article at PubMed) PMID:25158758
DOI: Full-text: DOI:10.1186/s12974-014-0144-0

BACKGROUND: Aberrant neuroinflammation is suspected to contribute to the pathogenesis of myriad neurological diseases. As such, determining the pathways that promote or inhibit glial activation is of interest. Activation of the surface glycoprotein T-cell immunoglobulin and mucin-domain containing protein 3 (Tim-3) by the lectin galectin-9 has been implicated in promoting innate immune cell activation by potentiating or synergizing toll-like receptor (TLR) signaling. In the present study we examined the role of the Tim-3/galectin-9 pathway in glial activation in vitro. METHOD: Primary monocultures of microglia or astrocytes, co-cultures containing microglia and astrocytes, and mixed glial cultures consisting of microglia, astrocytes and oligodendrocytes were stimulated with poly(I:C) or LPS, and galectin-9 up-regulation was determined. The effect of endogenous galectin-9 production on microglial activation was examined using cultures from wild-type and Lgals9 null mice. The ability for recombinant galectin-9 to promote microglia activation was also assessed. Tim-3 expression on microglia and BV2 cells was examined by qPCR and flow cytometry and its necessity in transducing the galectin-9 signal was determined using a Tim-3 specific neutralizing antibody or recombinant soluble Tim-3. RESULT: Astrocytes potentiated TNF production from microglia following TLR stimulation. Poly(I:C) stimulation increased galectin-9 expression in microglia and microglial-derived factors promoted galectin-9 up-regulation in astrocytes. Astrocyte-derived galectin-9 in turn enhanced microglial TNF production. Similarly, recombinant galectin-9 enhanced poly(I:C)-induced microglial TNF and IL-6 production. Inhibition of Tim-3 did not alter TNF production in mixed glial cultures stimulated with poly(I:C). CONCLUSION: Galectin-9 functions as an astrocyte-microglia communication signal and promotes cytokine production from microglia in a Tim-3 independent manner. Activation of CNS galectin-9 likely modulates neuroinflammatory processes in which TNF and IL-6 contribute to either pathology or reparation.

Annotation

Gene Ontology Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 10054077
Created: 2015-07-25
Species: All species
Last Modified: 2015-07-25
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.