Inhibition of psoriatic cell proliferation in in vitro skin models by amiprilose hydrochloride

Abstract

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.

The Development and Characterization of an In Vitro Model of Psoriasis

“…Animal models, however, can prove unsatisfactory, as allogeneic differences can cause artifactual immune responses, furnished by the xenograph, which may differ from that of psoriasis. Various attempts to model aspects of the disease in vitro have been reported, using both monolayer and stratified keratinocyte cultures (Saiag et al, 1985;Chapman et al, 1990;Mils et al, 1994;Van Ruissen et al, 1996a, b;Pol et al, 2002). Some previous studies have demonstrated the importance of crosstalk between the keratinocyte and the fibroblast in modeling the disease in vitro (Krueger and Jorgensen, 1990;Konstantinova et al, 1996;Krueger and Jorgensen, 1997).…”

Effect of hyperbaric oxygen on human skin cells in culture and in human dermal and skin equivalents

“…Development of “tissue equivalents,” as in vitro models of living tissue, provides an opportunity to study some of these processes in a more systematic and quantifiable fashion. We have developed a noncontracting human skin equivalent (HSE, NexMed, Inc., Robinsville NJ), 24 which has proven an invaluable tool in evaluation of potential topical pharmaceutical agents 25,26 . A particularly useful feature of our model is its translucence which allows the status of the cellular and extracellular components to be evaluated nonintrusively by light microscopy.…”

“…We have developed a noncontracting human skin equivalent (HSE, NexMed, Inc., Robinsville NJ), 24 which has proven an invaluable tool in evaluation of potential topical pharmaceutical agents. 25,26 A particularly useful feature of our model is its translucence which allows the status of the cellular and extracellular components to be evaluated nonintrusively by light microscopy. The goal of the studies described here was to utilize human cell monolayers as well as dermal and skin equivalents (DEs and SEs) to evaluate systematically the cellular and molecular responses to hyperbaric oxygen.…”

In Vivo and In Vitro Models of Psoriasis

“…Psoriasis is characterized by red and scaly plaques on the skin with a predilection for certain areas (elbows, knees and scalp) (Chapman et al, 1990;Lowes, et al, 2007). There are five clinical variants of psoriasis: guttate, erythrodermic, pustular, inverse and psoriasis vulgaris, the last of wich is the most common type seen in approximately 90% of patients (Fitzpatrick and Wolff, 2008).…”