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J Neurochem. 2013 Jun;125(6):803-8. doi: 10.1111/jnc.12250. Epub 2013 Apr 22.

WNT-3A and WNT-5A counteract lipopolysaccharide-induced pro-inflammatory changes in mouse primary microglia.

Author information

  • 1Department of Physiology & Pharmacology, Sec Receptor Biology & Signaling, Karolinska Institutet, Stockholm, Sweden.

Abstract

Surveying microglia, the resident macrophage-like cells in the central nervous system, continuously screen their surroundings to sense imbalance in tissue homeostasis. Their activity is tightly regulated in both a pro- and anti-inflammatory manner. We have previously shown that the lipoglycoproteins WNT-3A and WNT-5A drive pro-inflammatory transformation in primary mouse microglia cells, arguing that WNTs have a role in the modulation of the central nervous system immune response. In this study, we address the effects of recombinant WNT-3A and WNT-5A on lipopolysaccharide (LPS)-activated mouse primary microglia to investigate the putative anti-inflammatory modulation of microglia by WNTs. While both WNT-3A and WNT-5A alone induce an up-regulation of cyclooxygenase 2 (COX2), a generic pro-inflammatory microglia marker, LPS exceeds these effects dramatically. However, combination of LPS and WNTs results in a dose-dependent decrease in LPS-induced cyclooxygenase 2 protein and mRNA expression. In conclusion, our data suggest that WNTs have a dual and context-dependent effect on microglia acting in a homeostatic pro- and anti-inflammatory manner.

© 2013 International Society for Neurochemistry.

PMID:
23534675
[PubMed - indexed for MEDLINE]
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