Overview of the regulation of cyclooxygenase-2 and 5-lipoxygenase expression by 4-hydroxynonenal. In short-term of incubation, HNE induces a panoply of signaling pathways-mediating PGE2 production through COX-2 upregulation. PGE2 negatively regulates 5-LOX and LTB4 productions. In long-term of incubation, the increase of 5-LOX and LTB4 levels could be due to a decrease in COX-2 and PGE2 levels caused by gradual HNE depletion. COX-2: cyclooxygenase-2; HNE: 4-hydroxynonenal; 5-LOX: 5-lipoxygenase; MAPK: mitogen-activated protein kinase; PGE2: prostaglandin E2.