Figure 6.

Schematic illustration of IL-4-mediated post-transcriptional control of Cox-1. In addition to the previously identified Jak/Stat6 pathway that is downstream of IL-4R, our studies suggested translational control of Cox-1 expression through the IL-4R, Fes, Akt, and mTORC axis to effect M2 polarization and resolution of helminth infection. Metformin-dependent activation of AMPK inhibited mTORC to decrease M2 macrophages in addition to Cox-1 translation which reduced 15d-PGJ₂ and subsequent PPARγ activation. Dotted lines represent post-transcriptional mechanisms of Cox-1 regulation downstream of mTORC that is yet to be identified.