Figure 7.

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.