Effect of GSK3 inhibition on the transcriptional signature of human alveolar macrophages

The remarkable plasticity of macrophages is tied to extracelular cues and their subsequently signaling pathways. The transcriptional factor MAFB is critical to prompt the aquisition of an anti-inflammatory phenotype in macrophages. As MAFB activity and stability is highly regulated by GSK3, we explored the molecular impact of blocking GSK3 on the gene expression profile of human alveolar macrophages (AMØ), whose development and gene expression profile is GM-CSF-dependent. GSK3 inhibition skewed the transcriptional profile of AMØ towards an anti-inflammatory phenotype. Overall design: mRNA profiles of human alveolar macrophages (AMØ) purifed from bronchoalveolar lavage fluid in presence or absence of 10 micromolar of GSK3 a/ß inhibitor (CHIR99021) for 24 hours.