Inhibition of psoriatic cell proliferation in in vitro skin models by amiprilose hydrochloride |
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Authors: | M Lynne Chapman S Dan Dimitrijevich Julia C Hevelone Dudley Goetz Jack Cohen Gary E Wise Robert W Gracy |
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Institution: | (1) Cytogerontology Laboratory, Department of Biochemistry, The University of North Texas/Texas College of Osteopathic Medicine, 3500 Camp Bowie Boulevard, 76107 Fort Worth, Texas |
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Abstract: | Summary 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.
Supported in part by research grants from the National Institutes of Health (AG01274), The R.A. Welch Foundation (B-0502),
The Texas, Advanced Technology and Research Program (Wound Healing and Aging #2147), and Greenwich Pharmaceuticals Inc. R.
W. G. is the recipient of a MERIT Award from the National Institute on Aging. |
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Keywords: | in vitro skin model psoriasis amiprilose hydrochloride antiproliferative effect human tissue equivalent |
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