Effect of GSK3 inhibition 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 blocking GSK3 on the gene expression profile in GM-CSF-primed human monocyte derived macrophages. GSK3 inhibition 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) in presence or absence of 10 micromolar of GSK3 a/ß inhibitor (CHIR99021) for 48 hours.