Project description:Identification of genes differentially expressed between human monocyte-macrophages generated in the presence of either GM-CSF (termed M1) or M-CSF (termed M2) and in the presence (+MTX) or absence (-) of methotrexate
Project description:Identification of genes differentially expressed between human monocyte-macrophages generated in the presence of either GM-CSF (termed M1) or M-CSF (termed M2) and in the presence (+MTX) or absence (-) of Methotrexate
Project description:Identification of genes differentially expressed between human monocyte-macrophages generated in the presence of either GM-CSF (termed M1) or M-CSF (termed M2)
Project description:Unstimulated (M0), M1-polarized (GM-CSF, LPS, IFNγ-stimulated), and M2-polarized (M-CSF, IL-4-stimulated) canine blood-derived macrophages were generated in vitro and investigated for differences in their transcriptome to create a basis for future investigations upon the role of macrophage polarization in dogs, a species, which has emerging importance for translational research.
Project description:Monocytes mature to macrophages in the presence of the lineage determining cytokine M-CSF. They can be further polarized into M1 or M2 macrophages with distinct functional properties. We used microarrays to detail the global programme of gene expression underlying macrophage maturation and polarization and identified distinct classes of up-regulated genes during this process. Experiment Overall Design: Freshly isolated monocytes were cultured in the presence of M-CSF for 7 days, and then polarized to M1 or M2 cells. The study includes Monocytes at day 0, macrophages at day 3 and 7, M1 and m2 polarized macrophages.
Project description:In recent years, the M-CSF and GM-CSF cytokines have been identified as opposing regulators of the inflammatory program. However, the two cytokines are simultaneously present in the inflammatory milieu, and it is not clear how cells integrate these signals. In order to understand the regulatory networks associated with the GM/M-CSF signaling axis we analyzed DNA methylation in human monocytes. Our results indicate that GM-CSF induces activation of the inflammatory program and extensive DNA methylation changes, while M-CSF-polarized cells are in a less differentiated state. This inflammatory program is mediated via JAK2 associated with the GM-CSF receptor and the downstream ERK signaling. However, PI3K signaling is associated with a negative regulatory loop of the inflammatory program and M-CSF autocrine signaling in GM-CSF-polarized monocytes. Our findings describe the regulatory networks associated with the GM/M-CSF signaling axis and how they contribute to the establishment of the inflammatory program associated with monocyte activation.
