Possible cross-regulation of the E prostanoid receptors.
Exposure to UVB induces an inflammatory response in the skin that results in high levels of cyclooxygenase-2 (COX-2) and its enzymatic product, prostaglandin E2 (PGE(2)). PGE(2) signals via one of four E prostanoid (EP) receptors, EP1-4, but the roles of each of these receptors in UVB-mediated inflammation and skin carcinogenesis have not been fully defined. Topical application of ONO-8713, an EP1 antagonist, reduced the acute inflammatory effects of UVB irradiation. This compound also reduced UVB-induced tumor formation by approximately 50%, suggesting that signaling of PGE(2) via the EP1 receptor may play a role in UVB-mediated inflammation and carcinogenesis. Our laboratory has demonstrated that the EP1 receptor localized to the suprabasal layers of the epidermis and the EP3 receptor was found in the basal keratinocytes of unirradiated murine skin. While UVB exposure induced no change in the localization of the EP1 receptor, the EP3 receptor was detected in all layers of the epidermis in response to UVB. In mice that were topically treated with ONO-8713, UVB-induced changes in EP3 localization were prevented. This alteration in EP3 receptor localization was not seen following topical application of the anti-inflammatory drug celecoxib, indicating that the effects of ONO-8713 were not because of its anti-inflammatory properties. These results suggest a previously undescribed interaction between the EP1 and EP3 receptors in the epidermis.
Tober
Kathleen L
KL
Department of Pathology, The Ohio State University, Columbus, Ohio 43210, USA.
Thomas-Ahner
Jennifer M
JM
Maruyama
Takayuki
T
Oberyszyn
Tatiana M
TM
D000818:Animals; D006801:Humans; D011453:Prostaglandins / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D012878:Skin Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
C545635:PTGER1 protein, human; C545647:PTGER3 protein, human; C545650:PTGER4 protein, human; D011453:Prostaglandins; C545636:Ptger1 protein, mouse; C545648:Ptger3 protein, mouse; C545651:Ptger4 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype