A proposed COX‐2 and PGE₂ receptor interaction in UV‐exposed mouse skin

The cyclooxygenases (COX-1 and COX-2) and the prostaglandins (PGs) they generate play a major role in the skin's response to sunlight. Sunlight, especially the ultraviolet B (UVB) component, induces COX-2 and increases PG levels. However, PGs can have both beneficial and adverse cutaneous effects. To elucidate the roles of the COXs and the PGs they generate in response to UVB exposure, experiments with the COX-1- and COX-2-deficient mice have provided insight into the specific roles of each isoform. Furthermore, because PGE(2) is the major PG produced following UV exposure and PGE(2) manifests its biological activity via four membrane receptors (EP1, EP2, EP3, EP4), elucidating contributions of these receptors is essential for understanding the roles of PGs in UVB-induced effects. In this review, we summarize recent findings from the COX-deficient mice showing how COX-2 generated PGE(2) acting via the receptors EP2 and EP4 could contribute to short term beneficial, but also contribute to long-term carcinogenic effects in response to UVB exposure.