Expression profiles of primary bone marrow derived mouse macrophages – untreated and treated with LPS or LPS+PGE. Mus musculus

The polarization of macrophages into an anti-inflammatory or regulatory phenotype plays an important role in resolving inflammation. PGE2 regulates macrophage polarization via a PKA dependent pathway. PKA phosphorylates SIKs, inhibiting their ability to phosphorylate CRTC3 in cells. This in turn allows CRTC3 to translocate to the nucleus where it acts as a co-activator with the transcription factor CREB to induce IL-10 transcription. In line with this we find that either genetic or pharmacological inhibition of SIKs mimics the effect of PGE2 on IL-10 production. We show here that PGE2, in combination with LPS, is able to promote a regulatory like phenotype in macrophages characterized by high expression of IL-10 as well as the regulatory markers SPHK1 and LIGHT. Overall design: Gene expression profiles of primary bone marrow derived mouse macrophages treated with LPS or LPS+PGE and untreated controls were generated using Affymetrix mouse gene 1.1 ST arrays. In total, 12 arrays were generated from the three groups (LPS, LPS+PGE and control) with 4-replicates in each group. One sample from LPS group was removed due to QC issues and the remaining 11 that were used in our analyses are submitted here.