Summary of mechanism of formation and action of 12- and 15-HETE-PEs generated by human monocytes and murine peritoneal macrophages. (A) HETE-PEs and KETE-PEs are already present in the membranes of IL-4–cultured monocytes and peritoneal macrophages, but their levels are elevated ∼ 2-fold on ionophore activation. Generation involves direct oxidation of membrane phospholipids. (B) In vitro, HETE-PEs inhibit TLR4 signaling, activate PPAR-γ transcriptional activity, and stimulate dissociation of PEBP1 from Raf. PHGPx indicates, phospholipid hydroperoxide glutathione peroxidase; PGDH, prostaglandin dehydrogenase; PEBP1, PE-binding protein-1; and AA, arachidonic acid.