Cynthia M. Jorgensen

Defined system to assess the in vitro induction of a psoriasis phenotype on normal keratinocytes by fibroblasts from psoriatic subjects

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.

Effects of Serum from Normal and Psoriatic Subjects on the Proliferation of Fibroblasts from Involved and Uninvolved Skin of Psoriatic Patients

Background: A framework hypothesis for the pathogenesis of psoriasis states that “there is an aberration throughout the skin of patients with psoriasis that is modified to disease expression by circulating factors.” Objective: A question to emerge from this hypothesis concerns whether fibroblasts could be more central to the aberration than other cells of the skin? This article focuses on the modulation of growth of fibroblasts from uninvolved and involved sites of patients with psoriasis as a function of the type of serum in which they are grown. Methods: Fibroblasts were generated from normal subjects and from involved and uninvolved sites of six untreated psoriatic subjects and their growth in vitro was assessed as a function of the type of serum (fetal bovine serum, normal human serum, and serum from psoriatic subjects) in which they are grown. Results: The data show (a) that fibroblasts from psoriatic subjects, especially from uninvolved sites, have an inherent capacity to proliferate at an enhanced rate relative to normal fibroblasts; (b) that this enhanced proliferation can be augmented by normal human serum and to a greater degree by serum from psoriatic subjects; (c) that ≈ 40% of the enhanced proliferation is secondary to the psoriasis serum phenotype; (d) that ≈ 30% of enhanced proliferation is secondary to the psoriasis fibroblast phenotype; and (e) that the magnitude of these features are independent of the severity of psoriasis, as assessed at the time of donation of biopsies for generation of test fibroblasts or of blood for serum. Conclusion: These data support the hypothesis that there is an aberration throughout the skin of patients with psoriasis (enhanced proliferation of fibroblasts in vitro, especially from uninvolved sites) that is modified by circulating factors (serum).