Metz Martin, Lammel Verena, Gibbs Bernhard F, Maurer Marcus
Department of Dermatology, University of Mainz, Germany.
Am J Pathol. 2006 Sep;169(3):815-22. doi: 10.2353/ajpath.2006.060037.
Endothelin (ET-1) has been shown to crucially contribute to UV-induced skin responses such as tanning. To test whether ET-1 is also involved in early cutaneous reactions to UV, we assessed ET-1 skin levels in UV-irradiated mice. In correlation with the levels of UV-induced skin inflammation, ET-1 concentrations increased substantially and continually. Moreover, blocking of ET-1 receptors (ETA) resulted in significantly decreased cutaneous inflammation following UV irradiation. When we assessed skin responses to ET-1 injections, we observed prominent mast cell degranulation and mast cell-dependent inflammation. Since mast cells also critically contributed to UV-induced inflammation, we determined the ET-1-dependent inflammatory response to UV in the absence and presence of these cells. Interestingly, ETA blockade did not decrease UV-induced inflammation in mast cell-deficient mice, unless these mice had been adoptively transferred with mast cells before irradiation. This indicates that skin inflammation due to UV irradiation is caused in part by ET-1 acting on skin mast cells.
内皮素(ET-1)已被证明对紫外线诱导的皮肤反应(如晒黑)起着关键作用。为了测试ET-1是否也参与紫外线引起的早期皮肤反应,我们评估了紫外线照射小鼠皮肤中ET-1的水平。与紫外线诱导的皮肤炎症水平相关,ET-1浓度大幅持续增加。此外,阻断ET-1受体(ETA)导致紫外线照射后皮肤炎症显著减轻。当我们评估皮肤对ET-1注射的反应时,我们观察到明显的肥大细胞脱颗粒和肥大细胞依赖性炎症。由于肥大细胞对紫外线诱导的炎症也起着关键作用,我们在有或没有这些细胞的情况下,确定了ET-1对紫外线的依赖性炎症反应。有趣的是,ETA阻断并没有降低肥大细胞缺陷小鼠的紫外线诱导炎症,除非这些小鼠在照射前已通过过继转移获得肥大细胞。这表明紫外线照射引起的皮肤炎症部分是由ET-1作用于皮肤肥大细胞引起的。