Defined System to Assess the in Vitro Induction of a Psoriasis Phenotype on Normal Keratinocytes by Fibroblasts from Psoriatic Subjects

Abstract

Background: Research has shown that involved as well as uninvolved skin of psoriatic subjects have an inherent defect that manifests, at a minimum, as nonapparent epidermal hyperplasia. Fibroblasts have been shown to regulate epidermal proliferation and differentiation; furthermore, fibroblasts from patients with psoriasis have altered growth, response, and mediator release when compared with normal. Objective: We conjectured that it might be possible to generate the enhanced epidermal proliferation inherent to psoriatic skin in vitro using a defined interactive culture system with cellular components from the skin of normal and psoriatic subjects. Methods: To reduce the variables whereby fibroblasts stimulate keratinocyte proliferation in vitro, a system was developed that does not permit direct contact between keratinocytes and fibroblasts, but does permit the exchange of media and mediators as well as an assessment of keratinocyte growth as a function of time. Fibroblasts from involved and uninvolved sites from biopsies of seven untreated psoriatic subjects were assessed for their effect on the growth of keratinocytes from normal subjects. Results: Analysis shows that five of seven fibroblast sources from involved sites and six of seven from uninvolved sites of psoriatic subjects induce normal keratinocytes to display enhanced outgrowth. Three of 14 fibroblast sources consistently do not induce this change. Fibroblasts from uninvolved sources are particularly effective, with a mean of 40 ± 8% (SD) more growth than with normal fibroblasts. Conclusion: It is concluded that fibroblasts from psoriatics can induce the phenotype of increased epidermal proliferation on normal keratinocytes via a soluble mediator in a defined system.