Role of SOCS1 and SOCS3 in macrophage activation. STAT1 and NFκB drive M1 polarization and SOCS1 can inhibit these pathways. SOCS3 can regulate TLR signaling and inhibits IL-6-induced STAT3 activation and SMAD3 and PI3K activity to action an appropriate destructive effect. STAT3, STAT6, and PI3K can drive M2 activation and SOCS3 inhibits STAT3 and PI3K. Pathways that trigger SOCS1 in macrophages include STAT1 and NFκB, while SOCS3 expression can be induced by STAT3, NFκB, NOTCH1, PI3K, and MAP kinase activation.