Figure 2.

Schematic comparing signaling cascades activated by EPO in microglia and macrophages. The role of EPO in macrophages and microglia has primarily been evaluated in the context of inflammatory state and cell survival, respectively. In macrophages, EPO activates JAK/STAT and Akt signaling, inhibits GSK-3β activity, modulates NF-κB p65, decreases levels of pro-inflammatory cytokines and iNOS, and promotes phagocytosis and M2 activation state polarization. In microglia, EPO promotes cell survival, inhibits GSK-3β activity, and increases NF-κB p65 via PI-3K/Akt while simultaneously activating the Wnt-1/β-catenin pathway that results in sequestration of NF-κB in the nucleus. EPO also decreases PSR levels, suggesting decreased phagocytosis.