Prostaglandin E2 is required for ultraviolet B-induced skin inflammation via EP2 and EP4 receptors.
Keratinocytes are the major target of sunlight, and they produce prostaglandin (PG) E(2) upon ultraviolet (UV) exposure. Although indomethacin, one of cyclooxygenase inhibitors, is known to suppress UV-induced acute skin inflammation, it remains uncertain whether endogenous PGE(2) is responsible for UV-induced skin inflammation, and which subtype of PGE(2) receptors mediates this process. UV-induced skin inflammation was investigated by using genetically and pharmacologically PGE(2) receptor-deficient mice. We applied UV-induced skin inflammation model to genetical and pharmacological PGE(2) receptor-deficient mice. We exposed UVB on these mice at 5 kJ/m(2), and examined the ear swelling and the histological findings. We also measured the blood flow using a laser doppler device to assess the intensity of UVB-induced inflammatory change. The UV-induced ear swelling at 48 h after exposure was significantly reduced in EP2(-/-), EP4(-/-) or wild-type mice treated with the EP4 antagonist compared to control mice. Consistently, inflammatory cell infiltration into the local skin, and local blood flow after UV exposure were significantly reduced by EP2 or EP4 signaling blockade. These data suggest that PGE(2)-EP2/EP4 signaling is mandatory in UV-induced acute skin inflammation, presumably by enhancing blood flow in the microenvironment.
Kabashima
Kenji
K
Department of Pharmacology, Kyoto University Graduate School of Medicine, Sakyo, Kyoto, Japan. kkabashi@med.uoeh-u.ac.jp
Nagamachi
Miyako
M
Honda
Tetsuya
T
Nishigori
Chikako
C
Miyachi
Yoshiki
Y
Tokura
Yoshiki
Y
Narumiya
Shuh
S
D000818:Animals; D015232:Dinoprostone / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology*; D015603:Keratinocytes / Q000276:immunology / Q000528:radiation effects*; D051379:Mice; D009281:Naphthalenes / Q000494:pharmacology; D010654:Phenylbutyrates / Q000494:pharmacology; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply / Q000276:immunology / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014664:Vasodilation / Q000276:immunology / Q000528:radiation effects
C487890:4-(4-cyano-2-(2-(4-fluoronaphthalen-1-yl)propionylamino)phenyl)butyric acid; D009281:Naphthalenes; D010654:Phenylbutyrates; C545651:Ptger4 protein, mouse; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015232:Dinoprostone; D007213:Indomethacin