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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Humans
  • Lipopolysaccharides / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects*
  • Microglia / immunology
  • Microglia / metabolism
  • Primary Cell Culture
  • Proto-Oncogene Proteins / pharmacology
  • RNA, Messenger / metabolism
  • Recombinant Proteins / pharmacology
  • Wnt Proteins / metabolism*
  • Wnt Proteins / pharmacology
  • Wnt-5a Protein
  • Wnt3A Protein / metabolism*
  • Wnt3A Protein / pharmacology


  • Lipopolysaccharides
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Recombinant Proteins
  • WNT5A protein, human
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt3A Protein
  • Wnt3a protein, mouse
  • Wnt5a protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2