皮肤炎症和增殖体外:微分外用糖皮质激素的作用效果和模式。

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兰格K, Kleuser B, Gysler,巴德,玛雅C, Scheidereit C,科特HC, Schafer-Korting M

皮肤炎症和增殖体外:微分外用糖皮质激素的作用效果和模式。

皮肤:皮肤杂志杂志》2000;3 - 4月13日(2):93 - 103。

PubMed ID

10754457 (在PubMed

]

文摘

强的松的nonhalogenated双酯,prednicarbate (PC),是第一个局部糖皮质激素和一种改进的效益/风险比验证临床体外。评估如果这是由于独特的特征的类固醇,创建一个新的化合物根据一个相同的概念,强的松17-ethylcarbonate, 21-phenylacetate (PEP),和新的卤代单酯desoximetasone 21-cinnamate (DCE)测试和与PC相比,desoximetasone (DM)和倍他米松17-valerate (BMV)。孤立包皮角质细胞为体外抗炎过程的调查的表皮,成纤维细胞的来源被用来调查atrophogenic潜力。炎症是引起TNFalpha,导致增加白介素1α(Il-1alpha)合成。量化的ELISA,所有药物显著降低Il-1alpha生产。但PC和BMV似乎特别有效,其次是DM和两个新的副产品,这显示较小的抗炎活性。糖皮质激素酯包括PEP迅速退化的角化细胞(85%在12 h)。因此,Il-1alpha mRNA的核糖核酸酶保护试验执行允许短暂孵化时间,从而减少生物降解。这个试验证实本地PC和BMV的抗炎效果。在相反的DCE和PEP不会降低Il-1alpha mRNA在很大程度上如此。因此PEP作为前体药物。 In fibroblasts, Il-1alpha and Il-6 syntheses indicate proliferation and inflammation, respectively. Whereas PC and PEP inhibited Il-1alpha and Il-6 production in fibroblasts only to a minor extent, cytokine synthesis was strongly affected by the conventional glucocorticoids BMV and DM, but also by DCE. The minor unwanted effect of PC and PEP on fibroblasts was also reflected by their low influence on cell proliferation as derived from (3)H-thymidine incorporation. Again, more pronounced antiproliferative features were seen with the halogenated glucocorticoids. In the following, the correlation between antiphlogistic effects in keratinocytes (suppression of Il-1alpha) and antiproliferative effects in fibroblasts (suppression of Il-1alpha and Il-6; (3)H-thymidine incorporation) was analyzed. Here, PC is revealed as the only glucocorticoid with an improved benefit/risk ratio. Native PEP is shown to be almost ineffective and DCE presents exactly the opposite features of PC. It is tempting to speculate if this is due to different glucocorticoid receptor subtypes or different signaling pathways in keratinocytes and fibroblasts.

DrugBank数据引用了这篇文章

药物靶点

药物	目标	类	生物	药理作用	行动
Desoximetasone	糖皮质激素受体	蛋白质	人类	是的	受体激动剂	细节