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WNT-3A and WNT-5A counteract lipopolysaccharide-induced pro-inflammatory changes in mouse primary microglia
Carina Halleskog1, Gunnar Schulte
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.
Insights
WNT proteins show a dual role in microglia immune responses. While WNTs can be pro-inflammatory, they also reduce inflammation markers like cyclooxygenase 2 (COX2) when combined with lipopolysaccharide (LPS).
Area of Science:
- Neuroimmunology
- Cellular Biology
Background:
- Microglia are key immune cells in the central nervous system, regulating tissue homeostasis.
- Microglia exhibit both pro- and anti-inflammatory activities.
- Previous research indicated WNT-3A and WNT-5A promote pro-inflammatory responses in microglia.
Purpose of the Study:
- To investigate the anti-inflammatory effects of WNT-3A and WNT-5A on lipopolysaccharide (LPS)-activated primary mouse microglia.
- To explore the dual role of WNT signaling in microglia immune modulation.
Main Methods:
- Treatment of primary mouse microglia with recombinant WNT-3A and WNT-5A.
- Activation of microglia using lipopolysaccharide (LPS).
- Analysis of cyclooxygenase 2 (COX2) protein and mRNA expression.
Main Results:
- WNT-3A and WNT-5A alone induced cyclooxygenase 2 (COX2) expression.
- LPS significantly increased COX2 expression compared to WNTs alone.
- Co-administration of WNTs with LPS resulted in a dose-dependent decrease in LPS-induced COX2 expression.
Conclusions:
- WNT proteins exhibit context-dependent effects on microglia.
- WNTs can exert both pro-inflammatory and anti-inflammatory roles in microglia.
- WNT signaling contributes to the homeostatic regulation of the central nervous system immune response.
