Chapman M L, Dimitrijevich S D, Hevelone J C, Goetz D, Cohen J, Wise G E, Gracy R W
Department of Biochemistry, University of North Texas/Texas College of Osteopathic Medicine, Fort Worth 76109.
In Vitro Cell Dev Biol. 1990 Oct;26(10):991-6. doi: 10.1007/BF02624474.
Amiprilose hydrochloride, a 3-substituted glucose derivative, was found to inhibit the proliferation of human fibroblasts and keratinocytes originating from psoriatic lesions. Fibroblasts and keratinocytes were obtained from skin biopsies of normal donors, and from the biopsies of active/involved and uninvolved sites of psoriatic donors. The cells were cultured as monolayers or as components of tissue equivalent models. Keratinocytes and fibroblasts originating from biopsies of psoriatically involved areas were shown to proliferate at a significantly higher rate than those derived from uninvolved areas. The antiproliferative effect of amiprilose hydrochloride was not observed with normal keratinocytes or fibroblasts from the skin of healthy donors or from uninvolved areas of psoriatic donors. Amiprilose hydrochloride was not cytotoxic to any of these cells at levels below 0.1%. The combination of the low cytotoxicity and the selective antiproliferative effect indicates that this compound may be a useful antipsoriatic agent. The use of monolayer cultures and tissue equivalent models in this study illustrates the utility of such a progressive strategy in the evaluation of potential topical pharmaceuticals.
盐酸氨吡咯司,一种3-取代葡萄糖衍生物,被发现可抑制源自银屑病皮损的人成纤维细胞和角质形成细胞的增殖。成纤维细胞和角质形成细胞取自正常供体的皮肤活检组织,以及银屑病供体的活动/受累部位和未受累部位的活检组织。这些细胞以单层形式或作为组织等效模型的组成部分进行培养。结果显示,源自银屑病受累区域活检组织的角质形成细胞和成纤维细胞的增殖速度明显高于源自未受累区域的细胞。对于来自健康供体皮肤或银屑病供体未受累区域的正常角质形成细胞或成纤维细胞,未观察到盐酸氨吡咯司的抗增殖作用。在浓度低于0.1%时,盐酸氨吡咯司对这些细胞均无细胞毒性。低细胞毒性和选择性抗增殖作用的结合表明,该化合物可能是一种有用的抗银屑病药物。本研究中单层培养和组织等效模型的使用说明了这种渐进策略在评估潜在局部用药物方面的实用性。