Effect of siRNA-mediated GSK3 knock-down on the transcriptional signature of human GM-CSF-dependent monocyte-derived macrophages

The functional versatility of macrophages is intrincately tied to factors such as their ontogeny and the specific tissue and extracellular environment. Monocyte-derived macrophages are oppositely instructed by M-CSF or GM-CSF. GM-CSF drives monocyte-derived macrophages towards heightened pro-inflammatory activity and the acquisition of the lung alveolar macrophage phenotype and gene profile whereas M-CSF gives rise to anti-inflammatory, pro-resolving, and immunosuppressive monocyte-derived macrophages. We explored the molecular impact of siRNA mediated knocking-down GSK3A, GSK3B or both (GSK3A/B) on the gene expression profile of GM-CSF-primed human monocyte derived macrophages. GSK3A/B knowdown skewed the transcriptional profile of GM-MØ towards an anti-inflammatory phenotype. Overall design: mRNA profiles of human macrophages differentiated with GM-CSF (GM-MØ) and transfected with siRNA control (siCNT), siRNA for GSK3A (siGSK3A), siRNA for GSK3B (siGSK3B) or both (siGSK3A and siGSK3B) and analyzed 72 hours later.