title: WNT-3A and WNT-5A counteract lipopolysaccharide-induced pro-inflammatory changes in mouse primary microglia.
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.
authors.affiliation: Department of Physiology & Pharmacology, Sec Receptor Biology & Signaling, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Halleskog
authors.forename: Gunnar
authors.initials: G
authors.lastname: Schulte
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D061251:Primary Cell Culture; D011518:Proto-Oncogene Proteins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D051153:Wnt Proteins / Q000378:metabolism* / Q000494:pharmacology; D000071818:Wnt-5a Protein; D060509:Wnt3A Protein / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; C438615:Wnt5a protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2