Prostaglandin E2 is required for ultraviolet B-induced skin inflammation via EP2 and EP4 receptors
Prostaglandin E2 is required for ultraviolet B-induced skin inflammation via EP2 and EP4 receptors
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DOI：
10.1038/labinvest.3700491
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发表时间：
2007-01-01
影响因子：
5
通讯作者：
Narumiya, Shuh
中科院分区：
文献类型：
--
作者：
Kabashima, Kenji;Nagamachi, Miyako;Narumiya, Shuh
角质形成细胞是阳光的主要目标，在紫外线(UV)照射下，它们会产生前列腺素(PG)E-2。尽管已知环氧合酶抑制剂吲哚美辛可以抑制紫外线诱导的急性皮肤炎症，但内源性PGE(2)是否与紫外线诱导的皮肤炎症有关，以及PGE(2)受体的哪一亚型介导了这一过程仍不确定。利用PGE(2)受体缺陷小鼠，从遗传学和药理学角度研究了紫外线诱导的皮肤炎症。我们将紫外线诱导的皮肤炎症模型应用于遗传和药理学PGE(2)受体缺陷小鼠。我们用5kJ/m(2)的UVB对这些小鼠进行照射，并检测其耳肿胀和组织学结果。我们还使用激光多普勒设备测量了血流量，以评估UVB诱导的炎症变化的强度。经EP4拮抗剂处理的EP2(-/-)、EP4(-/-)和野生型小鼠暴露后48h的耳肿胀明显低于对照组。EP2或EP4信号传导阻断后，局部皮肤的炎性细胞浸润和局部血流量显著减少。这些数据表明，PGE(2)-EP2/EP4信号在紫外线诱导的急性皮肤炎中是强制性的，可能是通过增强微环境中的血液流动。
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.