Inhibition of psoriatic cell proliferation in in vitro skin models by amiprilose hydrochloride.
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.
Chapman
M L
ML
Department of Biochemistry, University of North Texas/Texas College of Osteopathic Medicine, Fort Worth 76109.
Dimitrijevich
S D
SD
Hevelone
J C
JC
Goetz
D
D
Cohen
J
J
Wise
G E
GE
Gracy
R W
RW
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000473:pathology; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000473:pathology; D011565:Psoriasis / Q000473:pathology*; D012266:Ribose / Q000031:analogs & derivatives; D012867:Skin / Q000166:cytology / Q000473:pathology
D012266:Ribose; D005944:Glucosamine; C018424:amiprilose