Figure 1.

Multiple factors regulate COX-2 expression. Estrogen (E₂), omega-3 PUFA and IL-1β promote COX-2 expression through the NF-κB signaling pathway. IL-1β stimulates the phosphorylation of MERK, p38 and JNK, then CRE and NF-κB p65 bind to sites on the COX-2 promoter to increase COX-2 expression. In hypoxic conditions, activated HIF-1α will suppress DUSP2 expression directly, and then result in the hypersensitivity of COX-2 in response to proinflammatory stimuli (e.g. IL-1β). Elevated NGF markedly upregulates the expression of PTGS2/COX-2 via the PI3K/AKT signaling pathway. Environmental pollutants, for example HCB and CB126, are known to act via the AhR. These organic compounds have some biological effects mediated by the activation of the cytosolic AhR complex (AhR-dioxin-c-Src), and regulate PTGS2 transcription indirectly. The combination of organic compounds and AhR induces HSD17B7 expression and results in the upregulation of E₂, IL-6 and IL-8, which will further promote COX-2 expression.